Objective: To determine the effect of flurbiprofen combined with prednisolone on interleukin-6 in elderly surgery patients. Methods: In this double-blind randomized controlled study, patients aged 65 to 80 who we...Objective: To determine the effect of flurbiprofen combined with prednisolone on interleukin-6 in elderly surgery patients. Methods: In this double-blind randomized controlled study, patients aged 65 to 80 who were undergoing spinal fusion surgery for disc herniation were administered flurbiprofen 100 mg (P group, flurbiprofen group), prednisolone 0.6 mg/kg (D group, prednisolone group), prednisolone 0.6 mg/kg plus flurbiprofen 100 mg (P + D group, flurbiprofen + prednisolone group) or normal saline (S group, saline group) 15 minutes before the induction of anesthesia. Plasma samples were collected before surgery (T0) and on day 1 (T1), day 2 (T2) and day 3 (T3) following surgery. At the same time, systemic inflammatory response syndrome (SIRS) was assessed by SIRS criteria. The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) for collected samples were measured. Results: Other groups had significantly lower levels of IL-6, CRP and occurrence of SIRS than S group (p < 0.05). Compared to groups P and D, the levels of IL-6 and CRP in P + D group were significantly lower on T1 (p < 0.05). Peak levels of IL-6 in all groups were presented on T1 (p 0.05). The levels of CRP within three days were significantly different but did not show peak levels (p > 0.05). Conclusion: Compared to prednisolone or flurbiprofen, combining flurbiprofen with prednisolone in elderly surgery patients led to an increased suppression of IL-6.展开更多
Objective:To investigate the relation between febrile convulsions and 25hydroxy-vitamin D_(3)[25-(OH)D_(3)]and interleukin-6(IL-6)levels in children.Methods:241 children(divided into simple febrile convulsions and com...Objective:To investigate the relation between febrile convulsions and 25hydroxy-vitamin D_(3)[25-(OH)D_(3)]and interleukin-6(IL-6)levels in children.Methods:241 children(divided into simple febrile convulsions and complex febrile convulsions),who were diagnosed with febrile convulsions at the Women and Children's Medical Center of Hainan Province from January 2017 to October 2022,were selected into the febrile convulsions group;100 healthy children,who had no uncomfortable symptoms and attended the outpatient clinic of the Women and Children's Medical Center of Hainan Province for physical examination,for the control group.All the subjects measured the serum 25-(OH)D_(3) and IL-6 levels,and clinical information,such as age,gender and season,was recorded.Results:1)Serum 25-(OH)D_(3) levels in the febrile convulsion group were significantly lower than in the healthy control group(78.77±20.37 nmol/L versus 96.55±29.74 nmol/L,respectively),and there was a statistically significant between the two groups(t value-6.359,P<0.001).Serum IL-6 levels in the febrile convulsion group were significantly higher than in the healthy control group,and there was a statistically significant between the two groups(Z value of-14.291,P<0.001).2)Serum 25-(OH)D_(3) levels in children with complex febrile convulsions were significantly lower than those in children with simple febrile convulsions,and the difference between the two groups was statistically significant(t-value of 6.612,P<0.05).IL-6 levels were higher in children with complex febrile convulsions than in children with simple febrile convulsions,and the difference between the two groups was statistically significant(Z value-10.151,P<0.001).The difference in the severity of febrile convulsions was statistically significant in serum 25-(OH)D_(3) levels(x^(2)=29.83,P<0.001).3)The results of correlation analysis showed that serum 25-(OH)D_(3) level was negatively correlated with febrile convulsion(γ=-0.393,P<0.05);serum 25-(OH)D_(3) level was positively correlated with that(γs=0.328,P<0.05).4)The correlation analysis results showed that the serum 25-(OH)D_(3) level was negatively correlated with the clinical characteristics of febrile convulsion(γ=-0.393,P<0.05).However,serum IL-6 water is positively correlated with it(γs=0.328,P<0.05).4)In contrast,there was no statistically significant difference in serum 25-(OH)D_(3) levels among children with febrile convulsions in different seasons(P>0.05).Conclusions:There is a correlation between febrile convulsion and serum levels of 25-(OH)D_(3) and IL-6.25-(OH)D_(3) and IL-6 may participate in the pathogenesis of febrile convulsion.展开更多
Metabolic syndrome (MetS) and its components have been linked to elevated serum levels of inflammatory biomarkers such as C-reactive protein, interleukin-6, interleukin-1β and tumor necrosis factor alpha. The aim of ...Metabolic syndrome (MetS) and its components have been linked to elevated serum levels of inflammatory biomarkers such as C-reactive protein, interleukin-6, interleukin-1β and tumor necrosis factor alpha. The aim of our study was to address the association between MetS components with serum hs-CRP and IL-6 levels among Congolese adults. A total of 357 participants (aged 30 - 87 years) were included in this cross-sectional study. Anthropometrics were collected and fasting blood sampled for assessment of fasting blood glycaemia (FBG), lipids and inflammatory parameters using commercially available assays. NCEP-ATPIII criteria were used to define MetS. The Median (IQR) hs-CRP and IL-6 levels were higher in participants with MetS than in those without ([7 (4, 14) versus 6 (4, 8)] mg/L;p = 0.092 and [23.8 (20.9, 27.6) versus 22.3 (19.5, 25.0)] pg/mL;p = 0.002). hs-CRP and IL-6 levels were significantly higher in females with MetS than in those without, but not in males. Among participants, only TG was correlated with hs-CRP (r = 0.149, p = 0.007), and a significant correlation was observed between TG (r = 0.116, p = 0.037), FBG (r = 0.208, p = 0.000), HDL-C (r = −0.119, p = 0.034) and SBP (r = 0.143, p = 0.010) and IL-6. In males, hs-CRP levels were positively correlated with TG (0.316;p = 0.000), negatively with HDL-C (r = −0.290, p = 0.0022), without such correlations in females. In Ames, IL-6 levels were positively correlated with FBG (r = 0.202;p = 0.035), and negatively with HDL-C (r = −0.249, p = 0.009). Significant correlations between IL-6 levels and FBG (r = 0.214;p = 0.000) or SBP (r = 0.227, p = 0.000) were observed in females. Logistic regression analysis was carried out to identify the relationship between MetS components and hs-CRP or IL-6. Values of area under receiver-operating characteristic (ROC) curves suggest potential use of serum hs-CRP (AUC = 0.675) and IL-6 (AUC = 0.656) as diagnostic biomarkers of MetS. Combination of hs-CRP and IL-6 improved diagnosis accuracy, yielding a 0.698 ROC curve area. MetS components are associated with hs-CRP and IL-6 levels among adults Congolese. Combining the two biomarkers hs-CRP and IL-6 improves Mets diagnostic accuracy compared to hs-CRP or IL-6 alone.展开更多
Since December 2019,a novel coronavirus that represents a serious threat to human lives has emerged.There is still no definite treatment for severe cases of the disease caused by this virus,named coronavirus disease 2...Since December 2019,a novel coronavirus that represents a serious threat to human lives has emerged.There is still no definite treatment for severe cases of the disease caused by this virus,named coronavirus disease 2019(COVID-19).One of the most considered treatment strategies targets the exaggerated immune regulator,and interleukin(IL)-6 is a crucial pro-inflammatory mediator.Severe acute respiratory syndrome coronavirus 2(SARSCoV-2)cases show an elevated level of IL-6 related to disease severity.IL-6 activity can be inhibited by the following:IL-6 itself,IL-6 signaling pathways such as Janus kinase and signal transducer and activator of transcription(JAK-STAT),gp130,IL-6R,and downstream activated ILs,such as IL-17 and IL-6 cytokine.Currently,according to these studies and their results,IL-6 blockade with anti-IL-6 or its receptor antibodies such as tocilizumab in COVID-19 is beneficial in severe cases and may reduce the mortality rate.JAK-STAT inhibitors block the cytokine storm by inhibiting several crucial pro-inflammatory mediators such as TNF-αand IL-6 and have shown various results in clinical trials.IL-6 induces IL-17 secretion,and IL-17 is involved in the pathogenesis of inflammatory processes.Clinical trials of anti-IL-17 drugs are currently recruiting,and anti-gp130 antibody is preclinical.However,this agent has shown positive effects in inflammatory bowel disease clinical trials and could be tested for SARS-CoV-2.This study aimed to review the role of IL-6 in the cytokine storm and studies regarding IL-6 and blockade of its inflammatory pathways in COVID-19 to determine if any of these agents are beneficial for COVID-19 patients.展开更多
AIM To determine the role of cartilage oligomeric matrix protein(COMP), interleukin(IL)-6, IL-10 and ratio of IL-6/IL-10 as risk factors of symptomatic lumbar osteoarthritis(OA) in postmenopausal women with estrogen d...AIM To determine the role of cartilage oligomeric matrix protein(COMP), interleukin(IL)-6, IL-10 and ratio of IL-6/IL-10 as risk factors of symptomatic lumbar osteoarthritis(OA) in postmenopausal women with estrogen deficiency.METHODS Case-control study had been conducted in Sanglah General Hospital from October 2015 until March 2016. The blood samples were obtained and analyzed by enzyme-linked immunosorbent assay(ELISA).RESULTS From 44 pairs of samples which divided into 44 samples as case group and 44 samples as control group showed that high level of COMP in estrogen deficiency postmenopausal women were not at risk(OR = 0.7; 95%CI: 0.261-1.751; P = 0.393) for symptomatic lumbar OA(cut-off point 0.946). Estrogen deficiency in postmenopausal women with the high level of IL-6 had 2.7 times risk(OR = 2.7; 95%CI: 0.991-8.320; P = 0.033) for symptomatic lumbar OA from the low level of IL-6(cut-off point 2.264). At lower level of IL-10, there was no risk for symptomatic lumbar OA(OR = 0.6; 95%CI: 0.209-1.798; P = 0.345) than with the higher level of IL-10(cut-off point 6.049). While the high ratio of IL-6/IL-10 level in estrogen deficiency postmenopausal women gave 3.4 times risk(OR = 3.4; 95%CI: 1.204-11.787; P = 0.011)for symptomatic lumbar OA than the low ratio of IL-6/IL-10 level(cut-off point 0.364).CONCLUSION High ratio of IL-6/IL-10 plasma level was the highest risk factor for causing symptomatic lumbar OA in postmenopausal women with estrogen deficiency.展开更多
Interleukin-6 (IL-6) is a pleiotropic cytokine which is expressed in many inflammatory cells in response to different types of stimuli, regulating a number of biological processes. The IL-6 gene is polymorphic in both...Interleukin-6 (IL-6) is a pleiotropic cytokine which is expressed in many inflammatory cells in response to different types of stimuli, regulating a number of biological processes. The IL-6 gene is polymorphic in both the 5' and 3' flanking regions and more than 150 single nucleotide polymorphisms have been identified so far. Genetic polymorphisms of IL-6 may affect the outcomes of several diseases, where the presence of high levels of circulating IL-6 have been correlated to the stage and/or the progression of the disease itself. The -174 G/C polymorphism is a frequent polymorphism, that is located in the upstream regulatory region of the IL-6 gene and affects IL-6 production. However, the data in the literature on the genetic association between the -174 G/C polymorphism and some specific liver diseases characterized by different etiologies are still controversial. In particular, most of the studies are quite unanimous in describing a correlation between the presence of the high-producer genotype and a worse evolution of the chronic liver disease. This is valid for patients with hepatitis C virus (HCV)-related chronic hepatitis and liver cirrhosis and hepatocellu-lar carcinoma (HCC) whatever the etiology. Studies in hepatitis B virus-related chronic liver diseases are not conclusive, while specific populations like non alcoholic fatty liver disease/non-alcoholic steatohepatitis, autoimmune and human immunodeficiency virus/HCV coinfected patients show a higher prevalence of the lowproducer genotype, probably due to the complexity of these clinical pictures. In this direction, a systematic revision of these data should shed more light on the role of this polymorphism in chronic liver diseases and HCC.展开更多
BACKGROUND: Pulmonary complications after orthoto- pic liver transplantation (OLT) include high morbidity and mortality. Experimental data have suggested hepatic ische- mia and reperfusion are induced by pro-inflammat...BACKGROUND: Pulmonary complications after orthoto- pic liver transplantation (OLT) include high morbidity and mortality. Experimental data have suggested hepatic ische- mia and reperfusion are induced by pro-inflammatory cyto- kines. The high level of inflammatory cytokines might ad- ditionally influence pulmonary cappillary fluid filtration. The objectives of this study were to measure the concentra- tions of tumor necrotic factor-alpha (TNF-α), interleukin- 6 (IL-6) and interleukin-8 (IL-8) during OLT and to in- vestigate the relationship between these cytokines and post- operative pulmonary complications. METHODS: Twenty-two patients undergoing OLT were divided into two groups according to whether they had postoperative pulmonary complications: group A consis- ting of 8 patients with postoperative pulmonary complica- tions , and group B consisting of 14 patients without post- operative pulmonary complications. Enzyme-linked im- munoassay (ELISA) was used to determine serum TNF-α, IL-6 and IL-8. Blood samples were taken at the beginning of operation (T0 ), clamping and cross-clamping of the in- ferior cava and portal vein (T1, T2 ), 90 minutes and 3 hours after reperfusion (T3 , T4 ) and 24 hours after opera- tion (T5). RESULTS: The level of PaO2/FiO2 in group A was lower than that in group B ( P <0. 05 ). The concentrations of TNF-α, IL-6 and IL-8 in the two groups increased rapidly at T2 , peaked at T3 , decreased rapidly after T3 until 24 hours after operation. The concentrations of TNF-α, IL-6 and IL-8 in group A were higher than those in group B at T2, T3, and T4(P<0.05). CONCLUSION: After un-clamping of the inferior cava and portal vein, the serum concentrations of TNF-α, IL-6 and IL-8 increased may be related to pulmonary injury after he- patic ischemic reperfusion.展开更多
AIM:To evaluate the role of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in cirrhotic patients who have hepatic and renal impairment with spontaneous bacterial peritonitis(SBP).METHODS:We prospectively stu...AIM:To evaluate the role of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in cirrhotic patients who have hepatic and renal impairment with spontaneous bacterial peritonitis(SBP).METHODS:We prospectively studied 120 cirrhotic patients with SBP and 80 cirrhotic patients with sterile ascitic fluid.They included 144 males and 56 females with ages ranging between 34 and 62 years.The diagnosis of cirrhosis was established by clinical and laboratory criteria that did not require histological confirmation.The severity of underlying liver disease was evaluated using Pugh's modification of Child's criteria(Child-Pugh scores).Ascitic fluid was sent to the laboratory for cell count,culture,sensitivity testing,and measurement of chemical elements(i.e.,albumin,glucose).Specimens were inoculated into aerobic and anaerobic blood culture bottles.Serum and ascitic fluid were also collected in sterile tubes at study entry(before the initiation of antibiotic treatment) and 48 h later.Assays for TNF-α and IL-6 in the serum and ascitic fluid were performed with an immunoenzymometric assay using manufacture's instructions.RESULTS:Cytokine levels in serum and ascitic fluid were significantly higher in the patients with SBP.(plasma TNF-α:135.35 ng/mL ± 11.21 ng/mL vs 92.86 ng/mL ± 17.56 ng/mL,P < 0.001;plasma IL-6:32.30 pg/mL ± 7.07 pg/mL vs 12.11 pg/mL ± 6.53 pg/mL,P < 0.001;ascitic fluid TNF-α:647.54 ± 107.11 ng/mL vs 238.43 ng/mL ± 65.42 ng/mL,P < 0.001);ascitic fluid IL-6:132.84 ng/mL ± 34.13 vs 40.41 ± 12.85 pg/mL,P < 0.001).About 48(40%) cirrhotic patients with SBP developed renal and hepatic impairment and showed significantly higher plasma and ascitic fluid cytokine levels at diagnosis of infection.[(plasma TNF-α:176.58 ± 17.84 vs 135.35 ± 11.21 ng/mL)(P < 0.001) and(IL-6:57.83 ± 7.85 vs 32.30 ± 7.07 pg/mL)(P < 0.001);ascitic fluid TNF-α:958.39 ± 135.72 vs 647.54 ± 107.11 ng/mL,(P < 0.001),ascitic fluid IL-6:654.74 ± 97.43 vs 132.84 ± 34.13 pg/mL,(P < 0.001)].Twenty nine patients(60.4%) with SBP and renal impairment died whereas,only four patients(5.55%) with SBP but without renal impairment died from gastrointestinal hemorrhage(P < 0.0005).CONCLUSION:It appears that TNF-α production may enhance liver cell injury and lead to renal impairment.This correlated well with the poor prognosis and significantly increased mortality associated with SBP in cirrhotic patients.展开更多
This study examined the role of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and cystatin C in ischemic stroke complicating atrial fibrillation (AF) and the relationship of systemic inflammation w...This study examined the role of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and cystatin C in ischemic stroke complicating atrial fibrillation (AF) and the relationship of systemic inflammation with this disease in order to identify AF patients who are at high risk of stroke and need optimal anticoagulant therapy.A total of 103 AF patients, simple (n=75) or complicated by ischemic stroke (n=28), and 112 control subjects were recruited.IL-6 level was detected by using enzyme linked immunosorbent assay.Cystatin C and hsCRP levels were measured by means of a particle-enhanced immunonephelometric assay.The results showed that the AF patients had higher levels of hsCRP (P=0.004), IL-6 (P=0.000), and cystatin C (P=0.000) than control subjects.Plasma hsCRP level was increased in the AF patients with ischemic stroke as compared to the patients with simple AF (P=0.036).The AF patients who had the level of hsCRP exceeding 3.83 mg/L were at a higher risk than those with hsCRP level lower than 3.83 mg/L (P=0.030).After adjusting for other factors, cystatin C remained positively associated with IL-6 (r=0.613) and hsCRP (r=0.488).It was concluded that hsCRP is positively correlated with ischemic stroke complicating AF and may be a risk factor independent of other risk factors for AF.Elevated cystatin C level is also indicative of the increased risk of AF.展开更多
BACKGROUND:The study aimed to evaluate the predictive role of interleukin-6(IL-6)and chronic obstructive pulmonary disease(COPD)assessment test(CAT)score in mechanical ventilation(MV)in COPD patients at the acute exac...BACKGROUND:The study aimed to evaluate the predictive role of interleukin-6(IL-6)and chronic obstructive pulmonary disease(COPD)assessment test(CAT)score in mechanical ventilation(MV)in COPD patients at the acute exacerbation stage in the emergency department(ED).METHODS:For a one-year period,among adult patients in the ED who met the criteria of acute exacerbation of COPD,158 who received MV within 48 hours after admission were compared to 294 who didn't require MV within the same period after admission.IL-6 level and CAT score were compared between the two groups.The predicted value of IL-6 and CAT score was assessed by logistic regression analysis and a receiver operating characteristic(ROC)curve.RESULTS:The IL-6 and CAT scores in the 158 MV patients were much higher than those without.IL-6 and CAT scores were independent predictors of MV within 48 hours using logistic regression analysis(IL-6:odds ratio[OR]1.053,95%confidence interval[CI]1.039–1.067,P<0.001;CAT score:OR 1.122,95%CI 1.086–1.159,P<0.001).The combination of IL-6 and CAT scores(area under ROC curve[AUC]0.826,95%CI 0.786–0.866,P<0.001)improved the accuracy of predicting MV within 48 hours when compared with IL-6(AUC 0.752,95%CI 0.703–0.800,P<0.001)and CAT scores alone(AUC 0.739,95%CI 0.692–0.786,P<0.001).The sensitivity and specificity were 69.6%,74.1%,75.32%and 63.6%,respectively.CONCLUSION:The combined of IL-6 and CAT scores is useful for evaluating the risk of COPD patients at acute exacerbation in ED,and can provide a predictive value for MV or not within 48 hours.展开更多
AIM To compare the expression levels of interleukin(IL)-6 in colorectal cancer(CRC) tissues and adjacent noncancerous tissues, and analyse the correlation of IL-6 expression with the clinicopathological parameters of ...AIM To compare the expression levels of interleukin(IL)-6 in colorectal cancer(CRC) tissues and adjacent noncancerous tissues, and analyse the correlation of IL-6 expression with the clinicopathological parameters of CRC. METHODS Fifty CRC tissue specimens and 50 matched adjacent mucosa specimens were collected. The expression of IL-6 in these clinical samples was examined by immunohistochemical staining. The correlation between IL-6 expression and clinicopathological parameters was assessed by statistical analysis.RESULTS IL-6 expression was significantly elevated in CRC tissues compared with noncancerous tissues(P < 0.001). IL-6 expression was positively correlated with tumour TNM stage(P < 0.001), but a negative correlation was detected between IL-6 expression and tumor histological differentiation in CRC(P < 0.05). Furthermore, IL-6 expression was associated with invasion depth and lymph node metastasis in CRC. CONCLUSION IL-6 might be a useful marker for predicting a poor prognosis in patients with CRC and might be used as a potential therapeutic target in CRC.展开更多
BACKGROUND Patients with hepatitis B virus-associated acute-on-chronic liver failure(HBVACLF)present a complex and poor prognosis.Systemic inflammation plays an important role in its pathogenesis,and interleukin-6(IL-...BACKGROUND Patients with hepatitis B virus-associated acute-on-chronic liver failure(HBVACLF)present a complex and poor prognosis.Systemic inflammation plays an important role in its pathogenesis,and interleukin-6(IL-6)as a pro-inflammatory cytokine is related with severe liver impairment and also plays a role in promoting liver regeneration.Whether serum IL-6 influences HBV-ACLF prognosis has not been studied.AIM To determine the impact of serum IL-6 on outcome of patients with HBV-ACLF.METHODS We performed a retrospective study of 412 HBV-ACLF patients.The findings were analyzed with regard to mortality and the serum IL-6 level at baseline,as well as dynamic changes of serum IL-6 within 4 wk.RESULTS The serum IL-6 level was associated with mortality.Within 4 wk,deceased patients had significantly higher levels of IL-6 at baseline than surviving patients[17.9(7.3-57.6)vs 10.4(4.7-22.3),P=0.011].Patients with high IL-6 levels(>11.8 pg/mL)had a higher mortality within 4 wk than those with low IL-6 levels(≤11.8 pg/mL)(24.2%vs 13.2%,P=0.004).The odds ratios calculated using univariate and multivariate logistic regression were 2.10(95%confidence interval[CI]:1.26-3.51,P=0.005)and 2.11(95%CI:1.15-3.90,P=0.017),respectively.The mortality between weeks 5 and 8 in patients with high IL-6 levels at 4 wk was 15.0%,which was significantly higher than the 6.6%mortality rate in patients with low IL-6 levels at 4 wk(hazard ratio=2.39,95%CI:1.05-5.41,P=0.037).The mortality was 5.0%in patients with high IL-6 levels at baseline and low IL-6 levels at 4 wk,7.5%in patients with low IL-6 levels both at baseline and at 4 wk,11.5%in patients with low IL-6 levels at baseline and high IL-6 levels at 4 wk,and 16.7%in patients with high IL-6 levels both at baseline and at 4 wk.The increasing trend of the mortality rate with the dynamic changes of IL-6 was significant(P for trend=0.023).CONCLUSION A high level of serum IL-6 is an independent risk factor for mortality in patients with HBV-ACLF.Furthermore,a sustained high level or dynamic elevated level of serum IL-6 indicates a higher mortality.展开更多
BACKGROUND The connection between inflammatory bowel disease(IBD)and colorectal cancer(CRC)is well-established,as persistent intestinal inflammation plays a substantial role in both disorders.Cytokines may further inf...BACKGROUND The connection between inflammatory bowel disease(IBD)and colorectal cancer(CRC)is well-established,as persistent intestinal inflammation plays a substantial role in both disorders.Cytokines may further influence the inflammation and the carcinogenesis process.AIM To compare cytokine patterns of active IBD patients with early and advanced CRC.METHODS Choosing a panel of cytokines crucial for Th17/Treg differentiation and behavior,in colon specimens,as mRNA biomarkers,and their serum protein levels.RESULTS We found a significant difference between higher gene expression of FoxP3,TGFb1,IL-10,and IL-23,and approximately equal level of IL-6 in CRC patients in comparison with IBD patients.After stratification of CRC patients,we found a significant difference in FoxP3,IL-10,IL-23,and IL-17A mRNA in early cases compared to IBD,and IL-23 alone in advanced CRC.The protein levels of the cytokines were significantly higher in CRC patients compared to IBD patients.CONCLUSION Our findings showed that IL-6 upregulation is essential for both IBD and CRC development until the upregulation of other Th17/Treg related genes(TGFb1,IL-10,IL-23,and transcription factor FoxP3)is a crucial primarily for CRC development.The significantly upregulated IL-6 could be a potential drug target for IBD and prevention of CRC development as well.展开更多
AIM:To determine the involvement of the interleukin(IL)-6 with the development of experimental subretinal fibrosis in a mouse model.METHODS:Subretinal fibrosis was induced by subretinal injection of macrophage-rich pe...AIM:To determine the involvement of the interleukin(IL)-6 with the development of experimental subretinal fibrosis in a mouse model.METHODS:Subretinal fibrosis was induced by subretinal injection of macrophage-rich peritoneal exudate cells and the local expression of IL-6 was assessed by quantitative real-time reverse transcriptionpolymerase chain reaction(RT-PCR)and enzyme-linked immunosorbent assay(ELISA)at various time points.In addition,we investigated the effect of IL-6 receptor(IL-6R)monoclonal antibody(MR16-1)on subretinal fibrosis development.RESULTS:IL-6 mRNA level was significantly elevated at 1d after subretinal fibrosis induction and increased further to about 12-fold at 2d,reaching the peak.The result of ELISA showed that IL-6 protein was not detected in naive mice.At 2d after subretinal fibrosis induction,IL-6 protein level was upregulated to 67.33±14.96 pg/mg in subretinal fibrosis mice.MR16-1treatment resulted in a reduced subretinal fibrosis area by 48%compared to animals from control group at 7d.CONCLUSION:Our results indicated that IL-6 signaling may contribute to the pathogenesis of subretinal fibrogenesis and IL-6R inhibition may provide an effective,novel treatment of advanced and late-stage neovascular age-related macular degeneration.展开更多
We present the case of a 53-year-old woman with long-standing ulcerative colitis and severe, steroid-dependent disease course unresponsive to treatment with azathioprine, methotrexate, anti-TNF antibodies(infliximab, ...We present the case of a 53-year-old woman with long-standing ulcerative colitis and severe, steroid-dependent disease course unresponsive to treatment with azathioprine, methotrexate, anti-TNF antibodies(infliximab, adalimumab) and tacrolimus, who refused colectomy as a therapeutic option. As the pro-inflammatory cytokine interleukin-6(IL-6) had been identified as a crucial regulator in the immunopathogenesis of inflammatory bowel diseases, we treated the patient with biweekly intravenous infusions of an anti-IL-6R antibody(tocilizumab) for 12 wk. However, no clinical improvement of disease activity was noted. In fact, endoscopic, histological and endomicroscopic assessment demonstrated exacerbation of mucosal inflammation and ulcer formation upon anti-IL-6R therapy. Mechanistic studies revealed that tocilizumab treatment failed to suppress intestinal IL-6 production, impaired epithelial barrier function and induced production of pro-inflammatory cytokines such as TNF, IL-21 and IFN-γ. Inhibition of IL-6 by tocilizumab had no clinical benefit in this patient with intractable ulcerative colitis and even led to exacerbation of mucosal inflammation. Our findings suggest that anti-IL-6R antibody therapy may leadto aggravation of anti-TNF resistant ulcerative colitis. When targeting IL-6, the differential responsiveness of target cells has to be taken into account, as IL-6 on the one side promotes acute and chronic mucosal inflammation via soluble IL-6R signaling but on the other side also strongly contributes to epithelial cell survival via membrane bound IL-6R signaling.展开更多
AIM:To investigate the effect of Tenascin C(TNC)on the expression of pro-inflammatory cytokines and matrixmetalloproteinases in human cardiac myofibroblasts(CMF).METHODS:CMF were isolated and cultured from patients un...AIM:To investigate the effect of Tenascin C(TNC)on the expression of pro-inflammatory cytokines and matrixmetalloproteinases in human cardiac myofibroblasts(CMF).METHODS:CMF were isolated and cultured from patients undergoing coronary artery bypass grafting.Cultured cells were treated with either TNC(0.1μmol/L,24 h)or a recombinant protein corresponding to different domains of the TNC protein;fibrinogen-like globe(FBG)and fibronectin typeⅢ-like repeats(TNⅢ5-7)(both 1μmol/L,24 h).The expression of the proinflammatory cytokines;interleukin(IL)-6,IL-1β,TNFαand the matrix metalloproteinases;MMPs(MMP1,2,3,9,10,MT1-MMP)was assessed using real time RT-PCR and western blot analysis.RESULTS:TNC increased both IL-6 and MMP3(P<0.01)mR NA levels in cultured human CMF but had no significant effect on the other markers studied.The increase in IL-6 mR NA expression was mirrored by an increase in protein secretion as assessed by enzymelinked immunosorbant assay(P<0.01).Treating CMF with the recombinant protein FBG increased IL-6mR NA and protein(P<0.01)whereas the recombinant protein TNⅢ5-7 had no effect.Neither FBG nor TNⅢ5-7 had any significant effect on MMP3 expression.The expression of toll-like receptor 4(TLR4)in human CMF was confirmed by real time RT-PCR,western blot and immunohistochemistry.Pre-incubation of cells with TLR4neutralising antisera attenuated the effect of both TNC and FBG on IL-6 mR NA and protein expression.CONCLUSION:TNC up-regulates IL-6 expression in human CMF,an effect mediated through the FBG domain of TNC and via the TLR4 receptor.展开更多
Previous studies reported the association between interleukin-6(IL-6)-174G/C gene polymorphism and the risk of diabetic nephropathy in type 2 diabetes mellitus(T2DN).However,the results remain controversial.In the pre...Previous studies reported the association between interleukin-6(IL-6)-174G/C gene polymorphism and the risk of diabetic nephropathy in type 2 diabetes mellitus(T2DN).However,the results remain controversial.In the present study,we conducted a meta-analysis to further examine this relationship between IL-6-174G/C gene polymorphism and T2DN.Three databases(PubMed,SinoMed and ISI Web of Science)were used to search clinical case-control studies about IL-6-174G/C polymorphism and T2DN published until Apr.14,2018.Fixed-or random-effects n lodels were used to calculate the effect sizes of odds ratio(OR)and 95%confide nee intervals(95%CI).Moreover,subgroup analysis was performed in tenns of the excretion rate of albuminuria.All the statistical analyses were con ducted using Stata 12.0.A total of 11 case-control studies were included in this study,involving 1203 cases of T2DN and 1571 cases of T2DM without DN.Metaanalysis showed that there was an association between IL-6-174G/C polymorphism and increased risk of T2DN under the allelic and recessive genetic models(G vs.C:OR=1.10,95%CI 1.03-1」&P=0.006;GG vs.CC+GC:OR=1.11,95%CI 1.02-1.21,P=0.016).In the subgroup analysis by albuminuria,a significant association of IL-6-174G/C polymorphism with risk of T2DN was noted in the microalbuminuria group under the recessive model(OR=1.54,95%CI 1.02-2.32,P=0.038).In conclusion,this meta-analysis suggests that IL-6-174G/C gene polymorphism is associated with the risk of T2DN.展开更多
AIM: To evaluate the effects of butein on inflammatory cytokines, matrix metalloproteinase-9(MMP-9), andcolitis in interleukin(IL)-10-/- mice.METHODS: To synchronize colitis, 8- to 10-wk-old IL-10-/- mice were fed pel...AIM: To evaluate the effects of butein on inflammatory cytokines, matrix metalloproteinase-9(MMP-9), andcolitis in interleukin(IL)-10-/- mice.METHODS: To synchronize colitis, 8- to 10-wk-old IL-10-/- mice were fed pellet-chow containing piroxicam for 2 wk. Subsequently, phosphate-buffered saline or butein(1 mg/kg per day, ip) was injected for 4 wk. Histologic scores, inflammatory cytokines, MMP-9 and phosphorylated signal transducer and activator of transcription 3(p STAT3) expressions were analyzed in IL-10-/- mice and in Colo 205 cells.RESULTS: Butein reduced the colonic inflammatory score by > 50%. Expression levels of IL-6, IL-1β, interferon(IFN)-γ and MMP-9 were decreased in the colons of mice exposed to butein, whereas other inflammatory cytokines(IL-17 A, IL-21 and IL-22) were unchanged. Immunohistochemical staining for p STAT3 and MMP-9 was significantly decreased in the buteintreated groups compared with the controls. Butein inhibited IL-6-induced activation of STAT3 in Colo 205 cells.CONCLUSION: Butein ameliorated colitis in IL-10-/-mice by regulating IL-6/STAT3 and MMP-9 activation.展开更多
BACKGROUND Inflammatory cytokines play a vital role in the occurrence of osteoarticular injury and inflammation. Whether inflammation-associated factors interleukin-1β(IL- 1β), IL-6, tumor necrosis factor-α(TNF-α)...BACKGROUND Inflammatory cytokines play a vital role in the occurrence of osteoarticular injury and inflammation. Whether inflammation-associated factors interleukin-1β(IL- 1β), IL-6, tumor necrosis factor-α(TNF-α) and vascular endothelial growth factor (VEGF) are involved in the pathogenesis of keen articular cartilage injury remains poorly understood. AIM To measure the levels of inflammatory factors [IL-1β, IL-6, TNF-α and VEGF] in patients with knee articular cartilage injury. METHODS Fifty-five patients with knee articular cartilage injury were selected as patient groups, who were divided into three grades [mild (n = 20), moderate (n = 19) and severe (n = 16)] according to disease severity and X-ray examinations. Meanwhile, 30 healthy individuals who underwent physical examination were selected as the control group. The levels of IL-1β, IL-6, TNF-α and VEGF were measured by ELISA and immunohistochemical staining. RESULTS Compared with the control group, patient groups displayed significantly higher levels of IL-1β, IL-6, TNF-α and VEGF, and the extent of increase was directly proportional to the severity of injury (P < 0.05). In addition, the number of cells with positive staining of IL-1β, IL-6, TNF-α and VEGF in the synovial membrane were significantly increased, along with increased disease severity (P < 0.05). After treatment, the scores of visual analogue scale and the Western Ontario and McMaster University of Orthopaedic Index in patient groups were 2.26 ± 1.13 and 15.56 ± 7.12 points, respectively, which were significantly lower than those before treatment (6.98 ± 1.32 and 49.48 ± 8.96). Correlation analysis suggested that IL-1β and TNF-α were positively correlated with VEGF. CONCLUSION IL-1β, IL-6, TNF-α and VEGF levels are increased in patients with knee articular cartilage injury, and are associated with the disease severity, indicating they might play an important role in the occurrence and development of knee articular cartilage injury. Furthermore, therapeutically targeting them might be a novel approach for the treatment of keen articular cartilage injury.展开更多
AIM: To investigate the protective efficacy of recombinant adenovirus containing hyper-interleukin-6(HyperIL-6, HIL-6) and hepatocyte growth factor(HGF)(AdHGF-HIL-6) compared to that of recombinant adenovirus containi...AIM: To investigate the protective efficacy of recombinant adenovirus containing hyper-interleukin-6(HyperIL-6, HIL-6) and hepatocyte growth factor(HGF)(AdHGF-HIL-6) compared to that of recombinant adenovirus containing either HIL-6 or HGF(Ad-HIL-6 or Ad-HGF) in rats with acute-on-chronic liver failure(ACLF).METHODS: The recombinant adenoviruses containing HIL-6 and/or HGF were constructed. We established an ACLF model, and rats were randomly assigned to control, model, Ad-GFP, Ad-HIL-6, Ad-HGF or AdHGF-HIL-6 group. We collected serum and liver tissue samples to test pathological changes, biochemical indexes and molecular biological indexes.RESULTS: Attenuated alanine aminotransferase, prothrombin time, high-mobility group box 1(HMGB1), endotoxin, tumour necrosis factor(TNF)-α and interferon-γ were observed in the Ad-HGF-, Ad-HIL-6- and Ad-HGFHIL-6-treated rats with ACLF. Likewise, reduced hepaticdamage and apoptotic activity, as well as reduced HMGB1 and Bax proteins, but raised expression of Ki67 and Bcl-2 proteins and Bcl-2/Bax ratio were also observed in the Ad-HGF-, Ad-HIL-6- and Ad-HGF-HIL-6-treated rats with ACLF. More significant changes were observed in the Ad-HGF-HIL-6 treatment group without obvious side effects. Furthermore, caspase-3 at the protein level decreased in the Ad-HIL-6 and Ad-HGFHIL-6 treatment groups, more predominantly in the latter group.CONCLUSION: This study identifies that the protective efficacy of Ad-HGF-HIL-6 is more potent than that of Ad-HGF or Ad-HIL-6 in ACLF rats, with no significant side effects.展开更多
文摘Objective: To determine the effect of flurbiprofen combined with prednisolone on interleukin-6 in elderly surgery patients. Methods: In this double-blind randomized controlled study, patients aged 65 to 80 who were undergoing spinal fusion surgery for disc herniation were administered flurbiprofen 100 mg (P group, flurbiprofen group), prednisolone 0.6 mg/kg (D group, prednisolone group), prednisolone 0.6 mg/kg plus flurbiprofen 100 mg (P + D group, flurbiprofen + prednisolone group) or normal saline (S group, saline group) 15 minutes before the induction of anesthesia. Plasma samples were collected before surgery (T0) and on day 1 (T1), day 2 (T2) and day 3 (T3) following surgery. At the same time, systemic inflammatory response syndrome (SIRS) was assessed by SIRS criteria. The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) for collected samples were measured. Results: Other groups had significantly lower levels of IL-6, CRP and occurrence of SIRS than S group (p < 0.05). Compared to groups P and D, the levels of IL-6 and CRP in P + D group were significantly lower on T1 (p < 0.05). Peak levels of IL-6 in all groups were presented on T1 (p 0.05). The levels of CRP within three days were significantly different but did not show peak levels (p > 0.05). Conclusion: Compared to prednisolone or flurbiprofen, combining flurbiprofen with prednisolone in elderly surgery patients led to an increased suppression of IL-6.
基金Hainan Province health industry scientific research project(No.21A200142)Hainan Province Clinical Medical Center(No QWYH202175)。
文摘Objective:To investigate the relation between febrile convulsions and 25hydroxy-vitamin D_(3)[25-(OH)D_(3)]and interleukin-6(IL-6)levels in children.Methods:241 children(divided into simple febrile convulsions and complex febrile convulsions),who were diagnosed with febrile convulsions at the Women and Children's Medical Center of Hainan Province from January 2017 to October 2022,were selected into the febrile convulsions group;100 healthy children,who had no uncomfortable symptoms and attended the outpatient clinic of the Women and Children's Medical Center of Hainan Province for physical examination,for the control group.All the subjects measured the serum 25-(OH)D_(3) and IL-6 levels,and clinical information,such as age,gender and season,was recorded.Results:1)Serum 25-(OH)D_(3) levels in the febrile convulsion group were significantly lower than in the healthy control group(78.77±20.37 nmol/L versus 96.55±29.74 nmol/L,respectively),and there was a statistically significant between the two groups(t value-6.359,P<0.001).Serum IL-6 levels in the febrile convulsion group were significantly higher than in the healthy control group,and there was a statistically significant between the two groups(Z value of-14.291,P<0.001).2)Serum 25-(OH)D_(3) levels in children with complex febrile convulsions were significantly lower than those in children with simple febrile convulsions,and the difference between the two groups was statistically significant(t-value of 6.612,P<0.05).IL-6 levels were higher in children with complex febrile convulsions than in children with simple febrile convulsions,and the difference between the two groups was statistically significant(Z value-10.151,P<0.001).The difference in the severity of febrile convulsions was statistically significant in serum 25-(OH)D_(3) levels(x^(2)=29.83,P<0.001).3)The results of correlation analysis showed that serum 25-(OH)D_(3) level was negatively correlated with febrile convulsion(γ=-0.393,P<0.05);serum 25-(OH)D_(3) level was positively correlated with that(γs=0.328,P<0.05).4)The correlation analysis results showed that the serum 25-(OH)D_(3) level was negatively correlated with the clinical characteristics of febrile convulsion(γ=-0.393,P<0.05).However,serum IL-6 water is positively correlated with it(γs=0.328,P<0.05).4)In contrast,there was no statistically significant difference in serum 25-(OH)D_(3) levels among children with febrile convulsions in different seasons(P>0.05).Conclusions:There is a correlation between febrile convulsion and serum levels of 25-(OH)D_(3) and IL-6.25-(OH)D_(3) and IL-6 may participate in the pathogenesis of febrile convulsion.
文摘Metabolic syndrome (MetS) and its components have been linked to elevated serum levels of inflammatory biomarkers such as C-reactive protein, interleukin-6, interleukin-1β and tumor necrosis factor alpha. The aim of our study was to address the association between MetS components with serum hs-CRP and IL-6 levels among Congolese adults. A total of 357 participants (aged 30 - 87 years) were included in this cross-sectional study. Anthropometrics were collected and fasting blood sampled for assessment of fasting blood glycaemia (FBG), lipids and inflammatory parameters using commercially available assays. NCEP-ATPIII criteria were used to define MetS. The Median (IQR) hs-CRP and IL-6 levels were higher in participants with MetS than in those without ([7 (4, 14) versus 6 (4, 8)] mg/L;p = 0.092 and [23.8 (20.9, 27.6) versus 22.3 (19.5, 25.0)] pg/mL;p = 0.002). hs-CRP and IL-6 levels were significantly higher in females with MetS than in those without, but not in males. Among participants, only TG was correlated with hs-CRP (r = 0.149, p = 0.007), and a significant correlation was observed between TG (r = 0.116, p = 0.037), FBG (r = 0.208, p = 0.000), HDL-C (r = −0.119, p = 0.034) and SBP (r = 0.143, p = 0.010) and IL-6. In males, hs-CRP levels were positively correlated with TG (0.316;p = 0.000), negatively with HDL-C (r = −0.290, p = 0.0022), without such correlations in females. In Ames, IL-6 levels were positively correlated with FBG (r = 0.202;p = 0.035), and negatively with HDL-C (r = −0.249, p = 0.009). Significant correlations between IL-6 levels and FBG (r = 0.214;p = 0.000) or SBP (r = 0.227, p = 0.000) were observed in females. Logistic regression analysis was carried out to identify the relationship between MetS components and hs-CRP or IL-6. Values of area under receiver-operating characteristic (ROC) curves suggest potential use of serum hs-CRP (AUC = 0.675) and IL-6 (AUC = 0.656) as diagnostic biomarkers of MetS. Combination of hs-CRP and IL-6 improved diagnosis accuracy, yielding a 0.698 ROC curve area. MetS components are associated with hs-CRP and IL-6 levels among adults Congolese. Combining the two biomarkers hs-CRP and IL-6 improves Mets diagnostic accuracy compared to hs-CRP or IL-6 alone.
文摘Since December 2019,a novel coronavirus that represents a serious threat to human lives has emerged.There is still no definite treatment for severe cases of the disease caused by this virus,named coronavirus disease 2019(COVID-19).One of the most considered treatment strategies targets the exaggerated immune regulator,and interleukin(IL)-6 is a crucial pro-inflammatory mediator.Severe acute respiratory syndrome coronavirus 2(SARSCoV-2)cases show an elevated level of IL-6 related to disease severity.IL-6 activity can be inhibited by the following:IL-6 itself,IL-6 signaling pathways such as Janus kinase and signal transducer and activator of transcription(JAK-STAT),gp130,IL-6R,and downstream activated ILs,such as IL-17 and IL-6 cytokine.Currently,according to these studies and their results,IL-6 blockade with anti-IL-6 or its receptor antibodies such as tocilizumab in COVID-19 is beneficial in severe cases and may reduce the mortality rate.JAK-STAT inhibitors block the cytokine storm by inhibiting several crucial pro-inflammatory mediators such as TNF-αand IL-6 and have shown various results in clinical trials.IL-6 induces IL-17 secretion,and IL-17 is involved in the pathogenesis of inflammatory processes.Clinical trials of anti-IL-17 drugs are currently recruiting,and anti-gp130 antibody is preclinical.However,this agent has shown positive effects in inflammatory bowel disease clinical trials and could be tested for SARS-CoV-2.This study aimed to review the role of IL-6 in the cytokine storm and studies regarding IL-6 and blockade of its inflammatory pathways in COVID-19 to determine if any of these agents are beneficial for COVID-19 patients.
文摘AIM To determine the role of cartilage oligomeric matrix protein(COMP), interleukin(IL)-6, IL-10 and ratio of IL-6/IL-10 as risk factors of symptomatic lumbar osteoarthritis(OA) in postmenopausal women with estrogen deficiency.METHODS Case-control study had been conducted in Sanglah General Hospital from October 2015 until March 2016. The blood samples were obtained and analyzed by enzyme-linked immunosorbent assay(ELISA).RESULTS From 44 pairs of samples which divided into 44 samples as case group and 44 samples as control group showed that high level of COMP in estrogen deficiency postmenopausal women were not at risk(OR = 0.7; 95%CI: 0.261-1.751; P = 0.393) for symptomatic lumbar OA(cut-off point 0.946). Estrogen deficiency in postmenopausal women with the high level of IL-6 had 2.7 times risk(OR = 2.7; 95%CI: 0.991-8.320; P = 0.033) for symptomatic lumbar OA from the low level of IL-6(cut-off point 2.264). At lower level of IL-10, there was no risk for symptomatic lumbar OA(OR = 0.6; 95%CI: 0.209-1.798; P = 0.345) than with the higher level of IL-10(cut-off point 6.049). While the high ratio of IL-6/IL-10 level in estrogen deficiency postmenopausal women gave 3.4 times risk(OR = 3.4; 95%CI: 1.204-11.787; P = 0.011)for symptomatic lumbar OA than the low ratio of IL-6/IL-10 level(cut-off point 0.364).CONCLUSION High ratio of IL-6/IL-10 plasma level was the highest risk factor for causing symptomatic lumbar OA in postmenopausal women with estrogen deficiency.
文摘Interleukin-6 (IL-6) is a pleiotropic cytokine which is expressed in many inflammatory cells in response to different types of stimuli, regulating a number of biological processes. The IL-6 gene is polymorphic in both the 5' and 3' flanking regions and more than 150 single nucleotide polymorphisms have been identified so far. Genetic polymorphisms of IL-6 may affect the outcomes of several diseases, where the presence of high levels of circulating IL-6 have been correlated to the stage and/or the progression of the disease itself. The -174 G/C polymorphism is a frequent polymorphism, that is located in the upstream regulatory region of the IL-6 gene and affects IL-6 production. However, the data in the literature on the genetic association between the -174 G/C polymorphism and some specific liver diseases characterized by different etiologies are still controversial. In particular, most of the studies are quite unanimous in describing a correlation between the presence of the high-producer genotype and a worse evolution of the chronic liver disease. This is valid for patients with hepatitis C virus (HCV)-related chronic hepatitis and liver cirrhosis and hepatocellu-lar carcinoma (HCC) whatever the etiology. Studies in hepatitis B virus-related chronic liver diseases are not conclusive, while specific populations like non alcoholic fatty liver disease/non-alcoholic steatohepatitis, autoimmune and human immunodeficiency virus/HCV coinfected patients show a higher prevalence of the lowproducer genotype, probably due to the complexity of these clinical pictures. In this direction, a systematic revision of these data should shed more light on the role of this polymorphism in chronic liver diseases and HCC.
文摘BACKGROUND: Pulmonary complications after orthoto- pic liver transplantation (OLT) include high morbidity and mortality. Experimental data have suggested hepatic ische- mia and reperfusion are induced by pro-inflammatory cyto- kines. The high level of inflammatory cytokines might ad- ditionally influence pulmonary cappillary fluid filtration. The objectives of this study were to measure the concentra- tions of tumor necrotic factor-alpha (TNF-α), interleukin- 6 (IL-6) and interleukin-8 (IL-8) during OLT and to in- vestigate the relationship between these cytokines and post- operative pulmonary complications. METHODS: Twenty-two patients undergoing OLT were divided into two groups according to whether they had postoperative pulmonary complications: group A consis- ting of 8 patients with postoperative pulmonary complica- tions , and group B consisting of 14 patients without post- operative pulmonary complications. Enzyme-linked im- munoassay (ELISA) was used to determine serum TNF-α, IL-6 and IL-8. Blood samples were taken at the beginning of operation (T0 ), clamping and cross-clamping of the in- ferior cava and portal vein (T1, T2 ), 90 minutes and 3 hours after reperfusion (T3 , T4 ) and 24 hours after opera- tion (T5). RESULTS: The level of PaO2/FiO2 in group A was lower than that in group B ( P <0. 05 ). The concentrations of TNF-α, IL-6 and IL-8 in the two groups increased rapidly at T2 , peaked at T3 , decreased rapidly after T3 until 24 hours after operation. The concentrations of TNF-α, IL-6 and IL-8 in group A were higher than those in group B at T2, T3, and T4(P<0.05). CONCLUSION: After un-clamping of the inferior cava and portal vein, the serum concentrations of TNF-α, IL-6 and IL-8 increased may be related to pulmonary injury after he- patic ischemic reperfusion.
文摘AIM:To evaluate the role of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in cirrhotic patients who have hepatic and renal impairment with spontaneous bacterial peritonitis(SBP).METHODS:We prospectively studied 120 cirrhotic patients with SBP and 80 cirrhotic patients with sterile ascitic fluid.They included 144 males and 56 females with ages ranging between 34 and 62 years.The diagnosis of cirrhosis was established by clinical and laboratory criteria that did not require histological confirmation.The severity of underlying liver disease was evaluated using Pugh's modification of Child's criteria(Child-Pugh scores).Ascitic fluid was sent to the laboratory for cell count,culture,sensitivity testing,and measurement of chemical elements(i.e.,albumin,glucose).Specimens were inoculated into aerobic and anaerobic blood culture bottles.Serum and ascitic fluid were also collected in sterile tubes at study entry(before the initiation of antibiotic treatment) and 48 h later.Assays for TNF-α and IL-6 in the serum and ascitic fluid were performed with an immunoenzymometric assay using manufacture's instructions.RESULTS:Cytokine levels in serum and ascitic fluid were significantly higher in the patients with SBP.(plasma TNF-α:135.35 ng/mL ± 11.21 ng/mL vs 92.86 ng/mL ± 17.56 ng/mL,P < 0.001;plasma IL-6:32.30 pg/mL ± 7.07 pg/mL vs 12.11 pg/mL ± 6.53 pg/mL,P < 0.001;ascitic fluid TNF-α:647.54 ± 107.11 ng/mL vs 238.43 ng/mL ± 65.42 ng/mL,P < 0.001);ascitic fluid IL-6:132.84 ng/mL ± 34.13 vs 40.41 ± 12.85 pg/mL,P < 0.001).About 48(40%) cirrhotic patients with SBP developed renal and hepatic impairment and showed significantly higher plasma and ascitic fluid cytokine levels at diagnosis of infection.[(plasma TNF-α:176.58 ± 17.84 vs 135.35 ± 11.21 ng/mL)(P < 0.001) and(IL-6:57.83 ± 7.85 vs 32.30 ± 7.07 pg/mL)(P < 0.001);ascitic fluid TNF-α:958.39 ± 135.72 vs 647.54 ± 107.11 ng/mL,(P < 0.001),ascitic fluid IL-6:654.74 ± 97.43 vs 132.84 ± 34.13 pg/mL,(P < 0.001)].Twenty nine patients(60.4%) with SBP and renal impairment died whereas,only four patients(5.55%) with SBP but without renal impairment died from gastrointestinal hemorrhage(P < 0.0005).CONCLUSION:It appears that TNF-α production may enhance liver cell injury and lead to renal impairment.This correlated well with the poor prognosis and significantly increased mortality associated with SBP in cirrhotic patients.
基金supported in part by grants from the National Natural Sciences Foundation of China (No.30700377)Wuhan International Cooperation Project (No.2008-70834407)
文摘This study examined the role of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and cystatin C in ischemic stroke complicating atrial fibrillation (AF) and the relationship of systemic inflammation with this disease in order to identify AF patients who are at high risk of stroke and need optimal anticoagulant therapy.A total of 103 AF patients, simple (n=75) or complicated by ischemic stroke (n=28), and 112 control subjects were recruited.IL-6 level was detected by using enzyme linked immunosorbent assay.Cystatin C and hsCRP levels were measured by means of a particle-enhanced immunonephelometric assay.The results showed that the AF patients had higher levels of hsCRP (P=0.004), IL-6 (P=0.000), and cystatin C (P=0.000) than control subjects.Plasma hsCRP level was increased in the AF patients with ischemic stroke as compared to the patients with simple AF (P=0.036).The AF patients who had the level of hsCRP exceeding 3.83 mg/L were at a higher risk than those with hsCRP level lower than 3.83 mg/L (P=0.030).After adjusting for other factors, cystatin C remained positively associated with IL-6 (r=0.613) and hsCRP (r=0.488).It was concluded that hsCRP is positively correlated with ischemic stroke complicating AF and may be a risk factor independent of other risk factors for AF.Elevated cystatin C level is also indicative of the increased risk of AF.
基金supported by grants from Dongzhimen Hospital Fund of Special Talent(2018RC01)Beijing University of Chinese Medicine Fund of Project(2019-JYB-XJSJJ-025)
文摘BACKGROUND:The study aimed to evaluate the predictive role of interleukin-6(IL-6)and chronic obstructive pulmonary disease(COPD)assessment test(CAT)score in mechanical ventilation(MV)in COPD patients at the acute exacerbation stage in the emergency department(ED).METHODS:For a one-year period,among adult patients in the ED who met the criteria of acute exacerbation of COPD,158 who received MV within 48 hours after admission were compared to 294 who didn't require MV within the same period after admission.IL-6 level and CAT score were compared between the two groups.The predicted value of IL-6 and CAT score was assessed by logistic regression analysis and a receiver operating characteristic(ROC)curve.RESULTS:The IL-6 and CAT scores in the 158 MV patients were much higher than those without.IL-6 and CAT scores were independent predictors of MV within 48 hours using logistic regression analysis(IL-6:odds ratio[OR]1.053,95%confidence interval[CI]1.039–1.067,P<0.001;CAT score:OR 1.122,95%CI 1.086–1.159,P<0.001).The combination of IL-6 and CAT scores(area under ROC curve[AUC]0.826,95%CI 0.786–0.866,P<0.001)improved the accuracy of predicting MV within 48 hours when compared with IL-6(AUC 0.752,95%CI 0.703–0.800,P<0.001)and CAT scores alone(AUC 0.739,95%CI 0.692–0.786,P<0.001).The sensitivity and specificity were 69.6%,74.1%,75.32%and 63.6%,respectively.CONCLUSION:The combined of IL-6 and CAT scores is useful for evaluating the risk of COPD patients at acute exacerbation in ED,and can provide a predictive value for MV or not within 48 hours.
基金Supported by the National Natural Science Foundation of China,No.81502131the Natural Science Foundation of Chongqing,No.cstc2016jcyj A0405the Scientific and Technological Research Program of Chongqing Municipal Education Commission,No.KJ1500332
文摘AIM To compare the expression levels of interleukin(IL)-6 in colorectal cancer(CRC) tissues and adjacent noncancerous tissues, and analyse the correlation of IL-6 expression with the clinicopathological parameters of CRC. METHODS Fifty CRC tissue specimens and 50 matched adjacent mucosa specimens were collected. The expression of IL-6 in these clinical samples was examined by immunohistochemical staining. The correlation between IL-6 expression and clinicopathological parameters was assessed by statistical analysis.RESULTS IL-6 expression was significantly elevated in CRC tissues compared with noncancerous tissues(P < 0.001). IL-6 expression was positively correlated with tumour TNM stage(P < 0.001), but a negative correlation was detected between IL-6 expression and tumor histological differentiation in CRC(P < 0.05). Furthermore, IL-6 expression was associated with invasion depth and lymph node metastasis in CRC. CONCLUSION IL-6 might be a useful marker for predicting a poor prognosis in patients with CRC and might be used as a potential therapeutic target in CRC.
基金Supported by National Thirteen Five-year Science and Technology Major Project of China,No.2018ZX10725506-002National Twelve Five-year Science and Technology Major Project of China,No.2012ZX10005-005.
文摘BACKGROUND Patients with hepatitis B virus-associated acute-on-chronic liver failure(HBVACLF)present a complex and poor prognosis.Systemic inflammation plays an important role in its pathogenesis,and interleukin-6(IL-6)as a pro-inflammatory cytokine is related with severe liver impairment and also plays a role in promoting liver regeneration.Whether serum IL-6 influences HBV-ACLF prognosis has not been studied.AIM To determine the impact of serum IL-6 on outcome of patients with HBV-ACLF.METHODS We performed a retrospective study of 412 HBV-ACLF patients.The findings were analyzed with regard to mortality and the serum IL-6 level at baseline,as well as dynamic changes of serum IL-6 within 4 wk.RESULTS The serum IL-6 level was associated with mortality.Within 4 wk,deceased patients had significantly higher levels of IL-6 at baseline than surviving patients[17.9(7.3-57.6)vs 10.4(4.7-22.3),P=0.011].Patients with high IL-6 levels(>11.8 pg/mL)had a higher mortality within 4 wk than those with low IL-6 levels(≤11.8 pg/mL)(24.2%vs 13.2%,P=0.004).The odds ratios calculated using univariate and multivariate logistic regression were 2.10(95%confidence interval[CI]:1.26-3.51,P=0.005)and 2.11(95%CI:1.15-3.90,P=0.017),respectively.The mortality between weeks 5 and 8 in patients with high IL-6 levels at 4 wk was 15.0%,which was significantly higher than the 6.6%mortality rate in patients with low IL-6 levels at 4 wk(hazard ratio=2.39,95%CI:1.05-5.41,P=0.037).The mortality was 5.0%in patients with high IL-6 levels at baseline and low IL-6 levels at 4 wk,7.5%in patients with low IL-6 levels both at baseline and at 4 wk,11.5%in patients with low IL-6 levels at baseline and high IL-6 levels at 4 wk,and 16.7%in patients with high IL-6 levels both at baseline and at 4 wk.The increasing trend of the mortality rate with the dynamic changes of IL-6 was significant(P for trend=0.023).CONCLUSION A high level of serum IL-6 is an independent risk factor for mortality in patients with HBV-ACLF.Furthermore,a sustained high level or dynamic elevated level of serum IL-6 indicates a higher mortality.
基金Supported by the Medical University of Sofia,No.22.2012-2013Trakia University of Stara Zagora,No.1.2016 and No.2.2017.
文摘BACKGROUND The connection between inflammatory bowel disease(IBD)and colorectal cancer(CRC)is well-established,as persistent intestinal inflammation plays a substantial role in both disorders.Cytokines may further influence the inflammation and the carcinogenesis process.AIM To compare cytokine patterns of active IBD patients with early and advanced CRC.METHODS Choosing a panel of cytokines crucial for Th17/Treg differentiation and behavior,in colon specimens,as mRNA biomarkers,and their serum protein levels.RESULTS We found a significant difference between higher gene expression of FoxP3,TGFb1,IL-10,and IL-23,and approximately equal level of IL-6 in CRC patients in comparison with IBD patients.After stratification of CRC patients,we found a significant difference in FoxP3,IL-10,IL-23,and IL-17A mRNA in early cases compared to IBD,and IL-23 alone in advanced CRC.The protein levels of the cytokines were significantly higher in CRC patients compared to IBD patients.CONCLUSION Our findings showed that IL-6 upregulation is essential for both IBD and CRC development until the upregulation of other Th17/Treg related genes(TGFb1,IL-10,IL-23,and transcription factor FoxP3)is a crucial primarily for CRC development.The significantly upregulated IL-6 could be a potential drug target for IBD and prevention of CRC development as well.
基金Supported by Liaoning Science and Technology Project(No.2013225303)
文摘AIM:To determine the involvement of the interleukin(IL)-6 with the development of experimental subretinal fibrosis in a mouse model.METHODS:Subretinal fibrosis was induced by subretinal injection of macrophage-rich peritoneal exudate cells and the local expression of IL-6 was assessed by quantitative real-time reverse transcriptionpolymerase chain reaction(RT-PCR)and enzyme-linked immunosorbent assay(ELISA)at various time points.In addition,we investigated the effect of IL-6 receptor(IL-6R)monoclonal antibody(MR16-1)on subretinal fibrosis development.RESULTS:IL-6 mRNA level was significantly elevated at 1d after subretinal fibrosis induction and increased further to about 12-fold at 2d,reaching the peak.The result of ELISA showed that IL-6 protein was not detected in naive mice.At 2d after subretinal fibrosis induction,IL-6 protein level was upregulated to 67.33±14.96 pg/mg in subretinal fibrosis mice.MR16-1treatment resulted in a reduced subretinal fibrosis area by 48%compared to animals from control group at 7d.CONCLUSION:Our results indicated that IL-6 signaling may contribute to the pathogenesis of subretinal fibrogenesis and IL-6R inhibition may provide an effective,novel treatment of advanced and late-stage neovascular age-related macular degeneration.
基金Supported by Clinical Research Group 257 CEDER of the Deutsche Forschungsgemeinschaft
文摘We present the case of a 53-year-old woman with long-standing ulcerative colitis and severe, steroid-dependent disease course unresponsive to treatment with azathioprine, methotrexate, anti-TNF antibodies(infliximab, adalimumab) and tacrolimus, who refused colectomy as a therapeutic option. As the pro-inflammatory cytokine interleukin-6(IL-6) had been identified as a crucial regulator in the immunopathogenesis of inflammatory bowel diseases, we treated the patient with biweekly intravenous infusions of an anti-IL-6R antibody(tocilizumab) for 12 wk. However, no clinical improvement of disease activity was noted. In fact, endoscopic, histological and endomicroscopic assessment demonstrated exacerbation of mucosal inflammation and ulcer formation upon anti-IL-6R therapy. Mechanistic studies revealed that tocilizumab treatment failed to suppress intestinal IL-6 production, impaired epithelial barrier function and induced production of pro-inflammatory cytokines such as TNF, IL-21 and IFN-γ. Inhibition of IL-6 by tocilizumab had no clinical benefit in this patient with intractable ulcerative colitis and even led to exacerbation of mucosal inflammation. Our findings suggest that anti-IL-6R antibody therapy may leadto aggravation of anti-TNF resistant ulcerative colitis. When targeting IL-6, the differential responsiveness of target cells has to be taken into account, as IL-6 on the one side promotes acute and chronic mucosal inflammation via soluble IL-6R signaling but on the other side also strongly contributes to epithelial cell survival via membrane bound IL-6R signaling.
文摘AIM:To investigate the effect of Tenascin C(TNC)on the expression of pro-inflammatory cytokines and matrixmetalloproteinases in human cardiac myofibroblasts(CMF).METHODS:CMF were isolated and cultured from patients undergoing coronary artery bypass grafting.Cultured cells were treated with either TNC(0.1μmol/L,24 h)or a recombinant protein corresponding to different domains of the TNC protein;fibrinogen-like globe(FBG)and fibronectin typeⅢ-like repeats(TNⅢ5-7)(both 1μmol/L,24 h).The expression of the proinflammatory cytokines;interleukin(IL)-6,IL-1β,TNFαand the matrix metalloproteinases;MMPs(MMP1,2,3,9,10,MT1-MMP)was assessed using real time RT-PCR and western blot analysis.RESULTS:TNC increased both IL-6 and MMP3(P<0.01)mR NA levels in cultured human CMF but had no significant effect on the other markers studied.The increase in IL-6 mR NA expression was mirrored by an increase in protein secretion as assessed by enzymelinked immunosorbant assay(P<0.01).Treating CMF with the recombinant protein FBG increased IL-6mR NA and protein(P<0.01)whereas the recombinant protein TNⅢ5-7 had no effect.Neither FBG nor TNⅢ5-7 had any significant effect on MMP3 expression.The expression of toll-like receptor 4(TLR4)in human CMF was confirmed by real time RT-PCR,western blot and immunohistochemistry.Pre-incubation of cells with TLR4neutralising antisera attenuated the effect of both TNC and FBG on IL-6 mR NA and protein expression.CONCLUSION:TNC up-regulates IL-6 expression in human CMF,an effect mediated through the FBG domain of TNC and via the TLR4 receptor.
文摘Previous studies reported the association between interleukin-6(IL-6)-174G/C gene polymorphism and the risk of diabetic nephropathy in type 2 diabetes mellitus(T2DN).However,the results remain controversial.In the present study,we conducted a meta-analysis to further examine this relationship between IL-6-174G/C gene polymorphism and T2DN.Three databases(PubMed,SinoMed and ISI Web of Science)were used to search clinical case-control studies about IL-6-174G/C polymorphism and T2DN published until Apr.14,2018.Fixed-or random-effects n lodels were used to calculate the effect sizes of odds ratio(OR)and 95%confide nee intervals(95%CI).Moreover,subgroup analysis was performed in tenns of the excretion rate of albuminuria.All the statistical analyses were con ducted using Stata 12.0.A total of 11 case-control studies were included in this study,involving 1203 cases of T2DN and 1571 cases of T2DM without DN.Metaanalysis showed that there was an association between IL-6-174G/C polymorphism and increased risk of T2DN under the allelic and recessive genetic models(G vs.C:OR=1.10,95%CI 1.03-1」&P=0.006;GG vs.CC+GC:OR=1.11,95%CI 1.02-1.21,P=0.016).In the subgroup analysis by albuminuria,a significant association of IL-6-174G/C polymorphism with risk of T2DN was noted in the microalbuminuria group under the recessive model(OR=1.54,95%CI 1.02-2.32,P=0.038).In conclusion,this meta-analysis suggests that IL-6-174G/C gene polymorphism is associated with the risk of T2DN.
基金Supported by Grants from the National Research Foundation of Korea,No.R1102452Korea University,No.K1220161by experimental techniques from the Core Laboratory for Convergent Translational Research of College of Medicine
文摘AIM: To evaluate the effects of butein on inflammatory cytokines, matrix metalloproteinase-9(MMP-9), andcolitis in interleukin(IL)-10-/- mice.METHODS: To synchronize colitis, 8- to 10-wk-old IL-10-/- mice were fed pellet-chow containing piroxicam for 2 wk. Subsequently, phosphate-buffered saline or butein(1 mg/kg per day, ip) was injected for 4 wk. Histologic scores, inflammatory cytokines, MMP-9 and phosphorylated signal transducer and activator of transcription 3(p STAT3) expressions were analyzed in IL-10-/- mice and in Colo 205 cells.RESULTS: Butein reduced the colonic inflammatory score by > 50%. Expression levels of IL-6, IL-1β, interferon(IFN)-γ and MMP-9 were decreased in the colons of mice exposed to butein, whereas other inflammatory cytokines(IL-17 A, IL-21 and IL-22) were unchanged. Immunohistochemical staining for p STAT3 and MMP-9 was significantly decreased in the buteintreated groups compared with the controls. Butein inhibited IL-6-induced activation of STAT3 in Colo 205 cells.CONCLUSION: Butein ameliorated colitis in IL-10-/-mice by regulating IL-6/STAT3 and MMP-9 activation.
文摘BACKGROUND Inflammatory cytokines play a vital role in the occurrence of osteoarticular injury and inflammation. Whether inflammation-associated factors interleukin-1β(IL- 1β), IL-6, tumor necrosis factor-α(TNF-α) and vascular endothelial growth factor (VEGF) are involved in the pathogenesis of keen articular cartilage injury remains poorly understood. AIM To measure the levels of inflammatory factors [IL-1β, IL-6, TNF-α and VEGF] in patients with knee articular cartilage injury. METHODS Fifty-five patients with knee articular cartilage injury were selected as patient groups, who were divided into three grades [mild (n = 20), moderate (n = 19) and severe (n = 16)] according to disease severity and X-ray examinations. Meanwhile, 30 healthy individuals who underwent physical examination were selected as the control group. The levels of IL-1β, IL-6, TNF-α and VEGF were measured by ELISA and immunohistochemical staining. RESULTS Compared with the control group, patient groups displayed significantly higher levels of IL-1β, IL-6, TNF-α and VEGF, and the extent of increase was directly proportional to the severity of injury (P < 0.05). In addition, the number of cells with positive staining of IL-1β, IL-6, TNF-α and VEGF in the synovial membrane were significantly increased, along with increased disease severity (P < 0.05). After treatment, the scores of visual analogue scale and the Western Ontario and McMaster University of Orthopaedic Index in patient groups were 2.26 ± 1.13 and 15.56 ± 7.12 points, respectively, which were significantly lower than those before treatment (6.98 ± 1.32 and 49.48 ± 8.96). Correlation analysis suggested that IL-1β and TNF-α were positively correlated with VEGF. CONCLUSION IL-1β, IL-6, TNF-α and VEGF levels are increased in patients with knee articular cartilage injury, and are associated with the disease severity, indicating they might play an important role in the occurrence and development of knee articular cartilage injury. Furthermore, therapeutically targeting them might be a novel approach for the treatment of keen articular cartilage injury.
基金Supported by Natural Science Foundation of Chongqing,No.cstc2012jj A10052Young High-End Medical Reserve Personnel Training Plan Foundation of Chongqing,China
文摘AIM: To investigate the protective efficacy of recombinant adenovirus containing hyper-interleukin-6(HyperIL-6, HIL-6) and hepatocyte growth factor(HGF)(AdHGF-HIL-6) compared to that of recombinant adenovirus containing either HIL-6 or HGF(Ad-HIL-6 or Ad-HGF) in rats with acute-on-chronic liver failure(ACLF).METHODS: The recombinant adenoviruses containing HIL-6 and/or HGF were constructed. We established an ACLF model, and rats were randomly assigned to control, model, Ad-GFP, Ad-HIL-6, Ad-HGF or AdHGF-HIL-6 group. We collected serum and liver tissue samples to test pathological changes, biochemical indexes and molecular biological indexes.RESULTS: Attenuated alanine aminotransferase, prothrombin time, high-mobility group box 1(HMGB1), endotoxin, tumour necrosis factor(TNF)-α and interferon-γ were observed in the Ad-HGF-, Ad-HIL-6- and Ad-HGFHIL-6-treated rats with ACLF. Likewise, reduced hepaticdamage and apoptotic activity, as well as reduced HMGB1 and Bax proteins, but raised expression of Ki67 and Bcl-2 proteins and Bcl-2/Bax ratio were also observed in the Ad-HGF-, Ad-HIL-6- and Ad-HGF-HIL-6-treated rats with ACLF. More significant changes were observed in the Ad-HGF-HIL-6 treatment group without obvious side effects. Furthermore, caspase-3 at the protein level decreased in the Ad-HIL-6 and Ad-HGFHIL-6 treatment groups, more predominantly in the latter group.CONCLUSION: This study identifies that the protective efficacy of Ad-HGF-HIL-6 is more potent than that of Ad-HGF or Ad-HIL-6 in ACLF rats, with no significant side effects.
