Objective:To analyze the value of D-dimer(D-D),interleukin-6(IL-6),and IL-18 in the differential diagnosis of children with refractory Mycoplasma pneumoniae pneumonia(RMPP).Methods:The medical records of 92 children w...Objective:To analyze the value of D-dimer(D-D),interleukin-6(IL-6),and IL-18 in the differential diagnosis of children with refractory Mycoplasma pneumoniae pneumonia(RMPP).Methods:The medical records of 92 children with Mycoplasma pneumoniae pneumonia(MPP)treated in the hospital were selected for retrospective analysis from January 2023 to January 2024.After comprehensive examinations such as computed tomography examination of the chest,48 children with general Mycoplasma pneumoniae pneumonia(GMPP)were put in the GMPP group and 44 children with RMPP were grouped in the RMPP group.The IL-6,IL-18,and D-D levels were compared between the two groups,and the receiver operating characteristic(ROC)curves were plotted to analyze their value for differential diagnosis of RMPP.Results:The levels of IL-6,IL-18,and D-D in the RMPP group were higher than those in the GMPP group(P<0.05);the ROC curves showed that the specificity of the differential diagnosis of IL-6,IL-18,and D-D was higher,and their diagnostic value was significant.Conclusion:Determination of IL-6,IL-18,and D-D levels in children with MPP can further diagnose the children’s condition,which can help physicians formulate targeted treatment plans,and is of great significance to the improvement of the children’s condition,which is worthy of attention.展开更多
AIM: To investigate the polymorphisms of interleukin-18 (IL-18) gene promoters, and to disclose whether such polymorphisms are associated with susceptibility to chronic hepatitis B in Chinese Han population. METHODS: ...AIM: To investigate the polymorphisms of interleukin-18 (IL-18) gene promoters, and to disclose whether such polymorphisms are associated with susceptibility to chronic hepatitis B in Chinese Han population. METHODS: Using polymerase chain reaction with sequence specific primers (PCR-SSP) method, the single nucleotide polymorphisms (SNPs) of the promoter region of IL-18 gene at position -607 and -137 were detected in 231 patients with chronic hepatitis B and 300 normal controls. RESULTS: Allele C at position -607 in the promoter of IL-18 gene was detected in 48.7% of normal controls and 51.9% of patients, while allele A at position -607 was detected in 51.3% of normal controls and 48.1% of patients. The frequencies of -607CC, -607 CA and -607AA genotypes in normal controls were 22.0%, 53.3% and 24.7% respectively and in chronic hepatitis B patients were 26.8%, 50.2% and 23.0% respectively. Allele G at position -137 in the promoter of IL-18 gene was detected in 82.3% of normal controls and 88.5% of chronic hepatitis B patients, while allele C at position -137 was detected in 17.7% of normal controls and 11.5% of patients. The frequencies of -137GG, GC and CC genotype were 67.3%, 30.0% and 2.7% in normal controls respectively, while in chronic hepatitis B patients were 78.8%, 19.5% and 1.7% respectively. The frequency of-137GG genotype in chronic hepatitis B groups was significantly higher than that in normal controls (x2=8.55, P=0.003 <0.05), whereas the frequencies of -607C/-137C and -607A/-137C haplotypes in chronic hepatitis B groups were significantly lower than that in normal controls. The association between genotypes of IL-18 promoter region polymorphisms and HBV copies showed that the frequency of -607AA genotype in high HBV-DNA copies groups was lower than that in low HBV-DNA copies groups (x2=6.03, P=0.014 <0.05). CONCLUSION: The polymorphisms of the promoter region of IL-18 gene at position -607 and -137 are closely associated with susceptibility to chronic hepatitis B. The people with allele C at position -137 in the promoter of IL-18 gene may be protected against HBV infection; moreover AA genotype at position -607 may be closely linked to inhibit HBV-DNA replication. These findings give some new clues to the study of pathogenesis of chronic hepatitis B.展开更多
AIM:To determine whether serum interleukin-18 (IL-18) levels correlated with clinicopathologic features and prognosis in patients with hepatocellular carcinoma (HCC). METHODS:Serum IL-18,IL-6 and IL-12 levels were mea...AIM:To determine whether serum interleukin-18 (IL-18) levels correlated with clinicopathologic features and prognosis in patients with hepatocellular carcinoma (HCC). METHODS:Serum IL-18,IL-6 and IL-12 levels were measured by enzyme-linked immunosorbent assay (ELISA) from 70 patients with HCC and 10 healthy controls. RESULTS:Serum IL-18,IL-6 and IL-12 levels of patients with HCC were significantly higher that those of the controls. The levels of IL-18 correlated significantly with the presence of venous invasion and advanced tumor stages classified by Okuda's criteria. Patients with high serum IL-18 levels (≥ 105 pg/mL) had a poorer survival than those with low serum IL-18 levels (< 105 pg/mL) (4 and 11 mo,respectively,P = 0.015). Multivariate analyses showed that serum IL-18 level,but not IL-6 and IL-12 levels,was a significant and independent prognostic factor of survival. CONCLUSION:These findings demonstrate that serum IL-8 may a useful biological marker of tumor invasiveness and an independent prognostic factor of survival for patients with HCC. Thus,the detailed mechanisms of IL-18 involving in tumor progression should be further investigated.展开更多
AIM: To explore the effect of intratumoral expressions of interleukin-12 (IL-12) and interleukin-18 (IL-18) on clinical features, angiogenesis and prognosis of gastric carcinoma. METHODS: The expressions of IL-12 and ...AIM: To explore the effect of intratumoral expressions of interleukin-12 (IL-12) and interleukin-18 (IL-18) on clinical features, angiogenesis and prognosis of gastric carcinoma. METHODS: The expressions of IL-12 and IL-18 from 50 samples of gastric cancer tissue were analyzed by immunohistochemistry, and microvessel density (MVD) was determined with microscopic imaging analysis system. RESULTS: The positive expression rates of IL-12 and IL-18 were 44% (22/50) and 26% (13/50), respectively. IL-12 was significantly associated with pathologic differentiation, depth of invasion, lymph node metastasis, distant metastasis, and TNM stage, and IL-18 was closely related to distant metastasis. Intratumoral IL-12 and IL-18 expressions were not statistically related to MVD scoring. IL-12-positive patients survived significantly longer than those with IL-12-negative tumors, but there was no significant difference between IL-18-positive patients and IL-18-negative ones. The multivariate analysis with Cox proportional hazard model revealed IL-12, MVD and T stage were independent prognostic factors. CONCLUSION: The positive expressions of IL-12 and IL-18 can play an important role in progression and metastasis of gastric cancer, and IL-12 might be an independent factor of poor prognosis in gastric carcinoma.展开更多
AIM:To investigate the correlation between interleukin-18(IL-18) gene polymorphisms and the risk of developing Crohn's disease(CD).METHODS:The PubMed,CISCOM,CINAHL,Web of Science,EBSCO,Cochrane Library,MEDLINE,EMB...AIM:To investigate the correlation between interleukin-18(IL-18) gene polymorphisms and the risk of developing Crohn's disease(CD).METHODS:The PubMed,CISCOM,CINAHL,Web of Science,EBSCO,Cochrane Library,MEDLINE,EMBASE and CBM databases were searched without any language restrictions using combinations of keywords relating to CD and IL-18 for relevant articles published before November 1st,2013.Screening of the published studies retrieved from searches was based on our stringent inclusion and exclusion criteria and resulted in seven eligible studies for meta-analysis.A metaanalysis was conducted using a random-effects model with STATA 12.0 software.Crude odds ratios(ORs) with95%confidence intervals(95%CI) were calculated.RESULTS:Seven case-control studies,with a total of1930 CD cases and 1930 healthy subjects,met our inclusion criteria.The results of our meta-analysis indicated that the IL-18 rs1946518 A>C and rs187238G>C polymorphisms may correlate with an increased risk of CD under five genetic models(all P < 0.05).Furthermore,we observed positive associations between the IL-18 rs360718 A>C polymorphism and CD risk under three genetic models(C allele vs A allele:OR = 2.03,95%CI:1.20-3.43,P = 0.008;CC vs AA+AC:OR = 2.39,95%CI:1.2-4.43,P = 0.006;CC vs AC:OR = 2.31,95%CI:1.22-4.38,P = 0.010).However,such associations were not found for the IL-18 rs917997 C>T,codon 35 A>C and rs1946519G>T polymorphisms(all P> 0.05).A subgroup analysis was conducted to investigate the effect of ethnicity on an individual's susceptibility to CD.Our results revealed positive correlations between IL-18 genetic polymorphisms and an increased risk of CD among Asians and Africans(all P < 0.05),but not among Caucasians(all P> 0.05).CONCLUSION:This meta-analysis indicated that the IL-18 rs1946518 A> C,rs187238 G>C and rs360718A>C polymorphisms may contribute to susceptibility to CD,especially among Asians and Africans.These polymorphisms are known to reduce IL-18 mRNA and protein levels.展开更多
To study the effect of interleukin-18 gene transfection on the tumorigenesis of breast cancer cell line Bacp37,human breast cancer cell line Bcap37 were transfected with Lipofectamine and selected by G418.The biologic...To study the effect of interleukin-18 gene transfection on the tumorigenesis of breast cancer cell line Bacp37,human breast cancer cell line Bcap37 were transfected with Lipofectamine and selected by G418.The biological expression of rhIL-18 was tested by RT-PCR and ELISA method;nude mice were injected with Bcap37 cell with or without the hIL-18 gene.The hIL-18 cDNA was successfully integrated into Bcap37 cell; 126.3±4.5pg hIL-18 secreted by one million transduced cells in 24 hours. Nude mice injected with IL-18 gene engineered Bcap37 cell had no tumor growth.These findings indicated that human breast cancer cells were successfully modified by the gene of IL-18 cytokine;the IL-18 gene engineered Bcap37 cells secreted hIL-18 and lost their tumorigenicity.The Bcap37 cells transduced with IL-18 gene may be used as breast cancer vaccine.展开更多
AIM: The aim of this study was to evaluate the association between ulcerative colitis activity and plasma or mucosal concentrations of interleukin (IL)-18. METHODS: 11-18 concentrations were measured in plasma and muc...AIM: The aim of this study was to evaluate the association between ulcerative colitis activity and plasma or mucosal concentrations of interleukin (IL)-18. METHODS: 11-18 concentrations were measured in plasma and mucosal samples from 15 patients with active ulcerative colitis (UC). RESULTS: The mean plasma concentration of IL-18 measured in all patients (422±88 pg/mL) doubled the mean value in healthy controls (206±32 pg/mL); however, the difference was not statistically significant. Plasma IL-18 levels revealed a significant positive correlation with scored endoscopic degree of mucosal injury, disease activity index, clinical activity index and C-reactive protein concentration. The mean concentration of plasma IL-18 was significantly higher in patients with severe ulcerative colitis (535±115 pg/mL) than in patients with mild ulcerative colitis (195±41 pg/mL), and in healthy controls. Although the mucosal mean IL-18 concentration in severe ulcerative colitis (2 523±618 pg/mg protein) doubled values observed in mild one (1347±308 pg/mg protein), there was no statistically significant difference. CONCLUSION: Plasma IL-18 can be considered as a surrogate marker helpful in evaluation of ulcerative colitis activity.展开更多
Objective:To investigate the effect of interleukin-18 (IL-18) on immune response induced by plasmid encoding hepatitis B virus middle protein antigen and to explore new strategies for prophylactic and therapeutic HBV ...Objective:To investigate the effect of interleukin-18 (IL-18) on immune response induced by plasmid encoding hepatitis B virus middle protein antigen and to explore new strategies for prophylactic and therapeutic HBV DNA vaccines.Methods:BALB/c mice were immunized with pCMV-M alone or co-immunized with pcDNA3-18 and pCMV-M and then their sera were collected for analysing anti-HBsAg antibody by ELISA;splenocytes were isolated for detecting specific CTL response and cytokine assay in vitro.Results:The anti-HBs antibody level of mice co-immunized with pcDNA3-18 and pCMV-M was slightly higher than that of mice immunized with pCMV-M alone,but there was not significantly different (P>0.05).Compared with mice injected with pCMV-M, the specific CTL cytotoxity activity of mice immunized with pcDNA3-18 and pCMV-M was significantly enhanced (P<0.05) and the level of IFN-γ in supernatant of splenocytes cultured with HBsAg in vitro was significantly elevated (P<0.05) while the level of IL-4 had no significant difference (P>0.05).Conclusion:The plasmid encoding IL-18 together with HBV M gene DNA vaccines may enhance specific TH1 cells and CTL cellular immune response induced in mice, so that IL-18 is a promising immune adjuvant.展开更多
AIM:To investigate the effects of rosiglitazone(RGZ) on expression of interleukin-18(IL-18) and caspase-1 in liver of non-alcoholic fatty liver disease(NAFLD) rats.METHODS:Twenty-eight Sprague-Dawley(SD) rats were ran...AIM:To investigate the effects of rosiglitazone(RGZ) on expression of interleukin-18(IL-18) and caspase-1 in liver of non-alcoholic fatty liver disease(NAFLD) rats.METHODS:Twenty-eight Sprague-Dawley(SD) rats were randomly divided into control,NAFLD,and RGZ treated NAFLD groups.A NAFLD rat model of NAFLD was established by feeding the animals with a high-fat diet for 12 wk.The NAFLD animals were treated with RGZ or vehicle for the last 4 wk(week 9-12) and then sacrificed to obtain liver tissues.Histological changes were analyzed with HE,oil red O and Masson's trichrome staining.Expressions of IL-18 and caspase-1 were detected using immunohistochemical staining and semi-quantitative reverse-transcription polymerase chain reaction(RT-PCR) analysis.RESULTS:The expression levels of both IL-18 and caspase-1 were higher in the liver of NAFLD group than in the control group.Steatosis,inflammation and fibrosis,found in the liver of NAFLD rats,were significantly improved 4 wk after RGZ treatment.The elevated hepatic IL-18 and caspase-1 expressions in NAFLD group were also significantly attenuated after RGZ treatment.CONCLUSION:RGZ treatment can ameliorate increased hepatic IL-18 production and histological changes in liver of NAFLD rats.The beneficial effects of RGZ on NAFLD may be partly due to its inhibitory effect on hepatic IL-18 production.展开更多
Objective： To investigate the relationship between serum interleukin-18 and interleukin-12 levels and clinicopathology of renal cell carcinoma. Methods： Peripheral blood samples were obtained from 20 healthy volunte...Objective： To investigate the relationship between serum interleukin-18 and interleukin-12 levels and clinicopathology of renal cell carcinoma. Methods： Peripheral blood samples were obtained from 20 healthy volunteers and 60 patients with renal cell carcinoma before curative surgery. IL-12 and IL-18 levels were determined by enzyme-linked immunosorbent assay. Results： Mean serum IL-12 and IL-18 levels were significantly higher in patients with renal cell carcinoma compared with healthy volunteers （P〈0.05） and mean serum IL-12 and IL-18 levels increased in patients as the pathologic stage progressed. A positive correlation was observed between serum IL-12 and IL-18 levels （P〈0.05）. In patients with renal cell carcinoma, increasing serum IL-12 and IL-18 levels correlated with pathological stage and Fuhrman grade. Conclusion： Serum IL-12 and IL-18 might be useful tumor markers in patients with renal cell carcinoma.展开更多
Objective： To investigate the effects of interleukin-18 （IL-18） on implanted Lewis lung cancer in suppressing angiogenesis and lymphangiogenesis. Methods： One week after hypodermic inoculation of Lewis cells, sixt...Objective： To investigate the effects of interleukin-18 （IL-18） on implanted Lewis lung cancer in suppressing angiogenesis and lymphangiogenesis. Methods： One week after hypodermic inoculation of Lewis cells, sixteen tumor-bearing syngeneic mice were randomly divided into two groups. The mice in the treatment group （group A） were intraperitoneally injected with the IL-18 and in the control group （group B） were intraperitoneally injected with normal saline for 7 days. The mice were killed on day 19. The morphology of the tumors was studied, the growth curve was described and the tumor inhibition rate was calculated. The numbers of metastasized pulmonary colonies were calculated using hematoxylin-eosin （HE） staining. The vascular endothelial growth factor A （VEGF-A）, vascular endothelial growth factor C （VEGF-C）, microvessel density （MVD） and lymphatic microvessel density （LMVD） in tumor mass were measured by immunohistochemistry staining （IHCS）. Results： In the group A, the tumor volume, tumor weigh, lung metastatic nodules, expression of VEGF-A and VEGF-C, MVD were all decreased significantly （P0.01 or P0.05）. The tumor inhibition rate was 75% and the inhibition rate of lung metastatic nodules was 61%. The LMVD in group A was also lower than group B, but without significant difference （P0.05）. Conclusion： IL-18 could suppress the tumor growth and metastasis of implanted Lewis lung cancer by way of down-regulating VEGF-A and VEGF-C expression, suppressing angiogenesis and lymphangiogenesis.展开更多
AIMTo assess circulatory levels of interleukin-18 (IL-18) and determine whether the presence of IL-18 promoter polymorphism influences metabolic syndrome phenotypes. METHODSThis study recruited one hundred and eighty ...AIMTo assess circulatory levels of interleukin-18 (IL-18) and determine whether the presence of IL-18 promoter polymorphism influences metabolic syndrome phenotypes. METHODSThis study recruited one hundred and eighty individuals divided into three groups with sixty subjects each as: Normal weight (18.0-22.9 kg/m<sup>2</sup>), overweight (23.0-25.9 kg/m<sup>2</sup>) and obese (> 26.0 kg/m<sup>2</sup>) according to South Asian criteria of BMI. Fasting blood glucose (FBG), Lipid profile, insulin, IL-18 and tumor necrosis factor (TNF)α were measured using ELISA kits, whereas low density lipoprotein (LDL)-cholesterol, insulin resistance (HOMA-IR) and insulin sensitivity (QUICKI) were calculated. The body fat percentage (BF) was measured through bioelectrical impedance analysis; waist and hip circumference were measured. Genotyping of IL-18 -607 C/A polymorphism was performed by using tetra-primer amplification refractory mutation system. Student t test, One-way analysis of variance, Hardy-Weinberg equilibrium, Pearson’s χ<sup>2</sup> test and Pearson’s correlation were used, where a P value < 0.05 was considered significant. RESULTSIn an aged matched study, obese subjects showed higher levels of FBG, cholesterol, triglycerides and LDL levels as compared to normal weight (P < 0.001). Highest levels of IL-18 and TNF levels were also seen in obese subjects (IL-18: 58.87 ± 8.59 ng/L) (TNF: 4581.93 ± 2132.05 pg/mL). The percentage of IL-18 -607 A/A polymorphism was higher in overweight and obese subjects vs normal weight subjects (P < 0.001). Moreover, subjects with AA genotype had a higher BF, insulin resistance, TNFα and IL-18 levels when compared with subjects with AC (heterozygous) or CC (wild type) genotypes. However, we did not find any difference in the lipid profile between three subgroups. CONCLUSIONThis preliminary data suggests that IL-18 polymorphism affects IL-18 levels that might cause low grade inflammation, further exacerbated by increased TNFα. All these increase the susceptibility to develop MetS. Further studies are required to validate our findings.展开更多
Objective： The aim of our study was to investigate the effects of interleukin-18 （IL-18） on implanted Lewis lung cancer in suppressing tumor growth and inducing tumor cells apoptosis. Methods： One week after hypod...Objective： The aim of our study was to investigate the effects of interleukin-18 （IL-18） on implanted Lewis lung cancer in suppressing tumor growth and inducing tumor cells apoptosis. Methods： One week after hypodermic inoculation of Lewis cells, sixteen tumor-bearing syngeneic mice were randomly divided into two groups. The mice in the treatment group were intrapedtoneal injected with the IL-18, in the control group were intrapedtoneal injected with normal saline. The health conditions of the mice were measured, the morphology of the tumors was studied and the apoptosis of implanted lung cancer cells was detected by TUNEL to evaluated the effects of IL-18. Results： IL-18 had no significant effects on the health condi- tions of the mice, but it could suppress the implanted tumor growth （inhibition rate was 75%） and induce tumor cells apoptosis. Conclusion： IL-18 can suppress the implanted Lewis lung cancer cells by way of inducing tumor cells apoptosis. It could be used as a new strategy for lung cancer.展开更多
Exposure to maternal stress during prenatal life is associated with an increased risk of neuropsychiatric disorders, such as depression and anxiety, in offspring. It has also been increasingly observed that prenatal s...Exposure to maternal stress during prenatal life is associated with an increased risk of neuropsychiatric disorders, such as depression and anxiety, in offspring. It has also been increasingly observed that prenatal stress alters the phenotype of offspring via immunological mechanisms and that immunological dysfunction, such as elevated interleukin-18 levels, has been reported in cultures of microglia. Prenatal restraint stress(PRS) in rats permits direct experimental investigation of the link between prenatal stress and adverse outcomes. However, the majority of studies have focused on the consequences of PRS delivered in the second half of pregnancy, while the effects of early prenatal stress have rarely been examined. Therefore, pregnant rats were subjected to PRS during early/middle and late gestation(days 8–14 and 15–21, respectively). PRS comprised restraint in a round plastic transparent cylinder under bright light(6500 lx) three times per day for 45 minutes. Differences in interleukin-18 expression in the hippocampus and in behavior were compared between offspring rats and control rats on postnatal day 75. We found that adult male offspring exposed to PRS during their late prenatal periods had higher levels of anxiety-related behavior and depression than control rats, and both male and female offspring exhibited higher levels of depression-related behavior, impaired recognition memory and diminished exploration of novel objects. Moreover, an elevated level of interleukin-18 was observed in the dorsal and ventral hippocampus of male and female early-and late-PRS offspring rats. The results indicate that PRS can cause anxiety and depression-related behaviors in adult offspring and affect the expression of interleukin-18 in the hippocampus. Thus, behavior and the molecular biology of the brain are affected by the timing of PRS exposure and the sex of the offspring. All experiments were approved by the Animal Experimentation Ethics Committee at Kunming Medical University, China(approval No. KMMU2019074) in January 2019.展开更多
Interleukin-18(IL-18) is a cytokine with many functions. This study was to investigate the serum levels of IL-18 and their clinical significance in patients with colore3ctaql carcinomas. Methods: Peripheral blood samp...Interleukin-18(IL-18) is a cytokine with many functions. This study was to investigate the serum levels of IL-18 and their clinical significance in patients with colore3ctaql carcinomas. Methods: Peripheral blood samples were obtained from 106 patients with colorectal carcinoma and 60 volunteers. The serum IL-18 levels were determined in each sample with an enzyme-linked immunosorbent assay (ELISA). Results: In patients before 1997, the mean IL-18 level was 338.46 pg/ml; in patients after 1997, the mean IL-18 level was 328.85 pg/ml, there is no evidence of loss of IL-18 immunoreactivity after prolonged storage at -80℃. The mean serum IL-18 level in 106 patients with colorectal carcinoma was significantly higher compared with the 60 healthy volunteers (P<0.05). Although the IL-18 level in patients with stage I did not differ from controls, the serum IL-18 levels of patients with stage II, stage III and stage IV disease were significantly higher compared with healthy control (P<0.05). The mean serum IL-18 level of patients with stage III disease, while the difference between patients with stage II and stage IV was not statistically significant (P>0.05). The survival rate of patients with IL-18 levels ≥346 pg/ml (n=47 patients) was significantly worse compared with patients who had IL-18 levels <346 pg/ml(n=57 patients). The 5-year-survival rates were 5.3% and 18.6%, respectively. Multivariate analysis using a Cox proportional hazards model identified the serum IL-18 level as an independent prognostic factor for survival Conclusion: The serum IL-18 level has a significant correlation with survival curve. The serum IL-18 level may represent a significant postoperative prognostic determinant in patients with colorectal carcinoma.展开更多
Objective: To investigate the effect of interleukin-12 (IL-12) and interleukin-18 (IL-18)DNA immunization on immune response induced by HIV-1 DNA vaccine and to explore new strategies for therapeutic HIV DNA vaccine. ...Objective: To investigate the effect of interleukin-12 (IL-12) and interleukin-18 (IL-18)DNA immunization on immune response induced by HIV-1 DNA vaccine and to explore new strategies for therapeutic HIV DNA vaccine. Methods: The recombinant expression vector pCI-neoGAG was constructed by inserting HIV Gag gene into the eukaryotic expression vector pCI-neo. Balb/c mice were immunized with pCI-neoGAG alone or co-immunized with the DNA encoding for IL-12 or IL-18.Anti-HIV antibody and IFN-γ were tested by ELISA,and splenocytes were isolated for detecting antigen-specific lymphoproliferative responses and specific CTL response by MTT assay and LDH assay respectively. Results: The anti-HIV antibody titers of mice co-immunized with pCI-neoGAG and the DNA encoding for IL-12 or IL-18 were lower than that of mice immunized with pCI-neoGAG alone(P<0.01). In contrast, the IFN-γ level of mice co-immunized with pCI-neoGAG and the DNA encoding for IL-12 or IL-18 was higher than that of mice immunized with pCI-neoGAG alone (P<0.01).Furthermore, compared with mice injected with pCI-neoGAG alone, the specific CTL cytotoxity activity and antigen-specific lymphoproliferative responses of mice immunized with pCI-neoGAG and the DNA encoding for IL-12 or IL-18 were significantly enhanced respectively (P<0.01). Conclusion: The DNA encoding for IL-12 or IL-18 together with HIV DNA vaccine may enhance specific Th-1 responses and cellular immune response elicited in mice. Hence, the DNA encoding for IL-12 or IL-18 are promising immune adjuvants for HIV-1 DNA vaccine.展开更多
文摘Objective:To analyze the value of D-dimer(D-D),interleukin-6(IL-6),and IL-18 in the differential diagnosis of children with refractory Mycoplasma pneumoniae pneumonia(RMPP).Methods:The medical records of 92 children with Mycoplasma pneumoniae pneumonia(MPP)treated in the hospital were selected for retrospective analysis from January 2023 to January 2024.After comprehensive examinations such as computed tomography examination of the chest,48 children with general Mycoplasma pneumoniae pneumonia(GMPP)were put in the GMPP group and 44 children with RMPP were grouped in the RMPP group.The IL-6,IL-18,and D-D levels were compared between the two groups,and the receiver operating characteristic(ROC)curves were plotted to analyze their value for differential diagnosis of RMPP.Results:The levels of IL-6,IL-18,and D-D in the RMPP group were higher than those in the GMPP group(P<0.05);the ROC curves showed that the specificity of the differential diagnosis of IL-6,IL-18,and D-D was higher,and their diagnostic value was significant.Conclusion:Determination of IL-6,IL-18,and D-D levels in children with MPP can further diagnose the children’s condition,which can help physicians formulate targeted treatment plans,and is of great significance to the improvement of the children’s condition,which is worthy of attention.
文摘AIM: To investigate the polymorphisms of interleukin-18 (IL-18) gene promoters, and to disclose whether such polymorphisms are associated with susceptibility to chronic hepatitis B in Chinese Han population. METHODS: Using polymerase chain reaction with sequence specific primers (PCR-SSP) method, the single nucleotide polymorphisms (SNPs) of the promoter region of IL-18 gene at position -607 and -137 were detected in 231 patients with chronic hepatitis B and 300 normal controls. RESULTS: Allele C at position -607 in the promoter of IL-18 gene was detected in 48.7% of normal controls and 51.9% of patients, while allele A at position -607 was detected in 51.3% of normal controls and 48.1% of patients. The frequencies of -607CC, -607 CA and -607AA genotypes in normal controls were 22.0%, 53.3% and 24.7% respectively and in chronic hepatitis B patients were 26.8%, 50.2% and 23.0% respectively. Allele G at position -137 in the promoter of IL-18 gene was detected in 82.3% of normal controls and 88.5% of chronic hepatitis B patients, while allele C at position -137 was detected in 17.7% of normal controls and 11.5% of patients. The frequencies of -137GG, GC and CC genotype were 67.3%, 30.0% and 2.7% in normal controls respectively, while in chronic hepatitis B patients were 78.8%, 19.5% and 1.7% respectively. The frequency of-137GG genotype in chronic hepatitis B groups was significantly higher than that in normal controls (x2=8.55, P=0.003 <0.05), whereas the frequencies of -607C/-137C and -607A/-137C haplotypes in chronic hepatitis B groups were significantly lower than that in normal controls. The association between genotypes of IL-18 promoter region polymorphisms and HBV copies showed that the frequency of -607AA genotype in high HBV-DNA copies groups was lower than that in low HBV-DNA copies groups (x2=6.03, P=0.014 <0.05). CONCLUSION: The polymorphisms of the promoter region of IL-18 gene at position -607 and -137 are closely associated with susceptibility to chronic hepatitis B. The people with allele C at position -137 in the promoter of IL-18 gene may be protected against HBV infection; moreover AA genotype at position -607 may be closely linked to inhibit HBV-DNA replication. These findings give some new clues to the study of pathogenesis of chronic hepatitis B.
基金Supported by the Rajadapiseksompoj research grant,Faculty of Medicine,Chulalongkorn University
文摘AIM:To determine whether serum interleukin-18 (IL-18) levels correlated with clinicopathologic features and prognosis in patients with hepatocellular carcinoma (HCC). METHODS:Serum IL-18,IL-6 and IL-12 levels were measured by enzyme-linked immunosorbent assay (ELISA) from 70 patients with HCC and 10 healthy controls. RESULTS:Serum IL-18,IL-6 and IL-12 levels of patients with HCC were significantly higher that those of the controls. The levels of IL-18 correlated significantly with the presence of venous invasion and advanced tumor stages classified by Okuda's criteria. Patients with high serum IL-18 levels (≥ 105 pg/mL) had a poorer survival than those with low serum IL-18 levels (< 105 pg/mL) (4 and 11 mo,respectively,P = 0.015). Multivariate analyses showed that serum IL-18 level,but not IL-6 and IL-12 levels,was a significant and independent prognostic factor of survival. CONCLUSION:These findings demonstrate that serum IL-8 may a useful biological marker of tumor invasiveness and an independent prognostic factor of survival for patients with HCC. Thus,the detailed mechanisms of IL-18 involving in tumor progression should be further investigated.
文摘AIM: To explore the effect of intratumoral expressions of interleukin-12 (IL-12) and interleukin-18 (IL-18) on clinical features, angiogenesis and prognosis of gastric carcinoma. METHODS: The expressions of IL-12 and IL-18 from 50 samples of gastric cancer tissue were analyzed by immunohistochemistry, and microvessel density (MVD) was determined with microscopic imaging analysis system. RESULTS: The positive expression rates of IL-12 and IL-18 were 44% (22/50) and 26% (13/50), respectively. IL-12 was significantly associated with pathologic differentiation, depth of invasion, lymph node metastasis, distant metastasis, and TNM stage, and IL-18 was closely related to distant metastasis. Intratumoral IL-12 and IL-18 expressions were not statistically related to MVD scoring. IL-12-positive patients survived significantly longer than those with IL-12-negative tumors, but there was no significant difference between IL-18-positive patients and IL-18-negative ones. The multivariate analysis with Cox proportional hazard model revealed IL-12, MVD and T stage were independent prognostic factors. CONCLUSION: The positive expressions of IL-12 and IL-18 can play an important role in progression and metastasis of gastric cancer, and IL-12 might be an independent factor of poor prognosis in gastric carcinoma.
文摘AIM:To investigate the correlation between interleukin-18(IL-18) gene polymorphisms and the risk of developing Crohn's disease(CD).METHODS:The PubMed,CISCOM,CINAHL,Web of Science,EBSCO,Cochrane Library,MEDLINE,EMBASE and CBM databases were searched without any language restrictions using combinations of keywords relating to CD and IL-18 for relevant articles published before November 1st,2013.Screening of the published studies retrieved from searches was based on our stringent inclusion and exclusion criteria and resulted in seven eligible studies for meta-analysis.A metaanalysis was conducted using a random-effects model with STATA 12.0 software.Crude odds ratios(ORs) with95%confidence intervals(95%CI) were calculated.RESULTS:Seven case-control studies,with a total of1930 CD cases and 1930 healthy subjects,met our inclusion criteria.The results of our meta-analysis indicated that the IL-18 rs1946518 A>C and rs187238G>C polymorphisms may correlate with an increased risk of CD under five genetic models(all P < 0.05).Furthermore,we observed positive associations between the IL-18 rs360718 A>C polymorphism and CD risk under three genetic models(C allele vs A allele:OR = 2.03,95%CI:1.20-3.43,P = 0.008;CC vs AA+AC:OR = 2.39,95%CI:1.2-4.43,P = 0.006;CC vs AC:OR = 2.31,95%CI:1.22-4.38,P = 0.010).However,such associations were not found for the IL-18 rs917997 C>T,codon 35 A>C and rs1946519G>T polymorphisms(all P> 0.05).A subgroup analysis was conducted to investigate the effect of ethnicity on an individual's susceptibility to CD.Our results revealed positive correlations between IL-18 genetic polymorphisms and an increased risk of CD among Asians and Africans(all P < 0.05),but not among Caucasians(all P> 0.05).CONCLUSION:This meta-analysis indicated that the IL-18 rs1946518 A> C,rs187238 G>C and rs360718A>C polymorphisms may contribute to susceptibility to CD,especially among Asians and Africans.These polymorphisms are known to reduce IL-18 mRNA and protein levels.
文摘To study the effect of interleukin-18 gene transfection on the tumorigenesis of breast cancer cell line Bacp37,human breast cancer cell line Bcap37 were transfected with Lipofectamine and selected by G418.The biological expression of rhIL-18 was tested by RT-PCR and ELISA method;nude mice were injected with Bcap37 cell with or without the hIL-18 gene.The hIL-18 cDNA was successfully integrated into Bcap37 cell; 126.3±4.5pg hIL-18 secreted by one million transduced cells in 24 hours. Nude mice injected with IL-18 gene engineered Bcap37 cell had no tumor growth.These findings indicated that human breast cancer cells were successfully modified by the gene of IL-18 cytokine;the IL-18 gene engineered Bcap37 cells secreted hIL-18 and lost their tumorigenicity.The Bcap37 cells transduced with IL-18 gene may be used as breast cancer vaccine.
文摘AIM: The aim of this study was to evaluate the association between ulcerative colitis activity and plasma or mucosal concentrations of interleukin (IL)-18. METHODS: 11-18 concentrations were measured in plasma and mucosal samples from 15 patients with active ulcerative colitis (UC). RESULTS: The mean plasma concentration of IL-18 measured in all patients (422±88 pg/mL) doubled the mean value in healthy controls (206±32 pg/mL); however, the difference was not statistically significant. Plasma IL-18 levels revealed a significant positive correlation with scored endoscopic degree of mucosal injury, disease activity index, clinical activity index and C-reactive protein concentration. The mean concentration of plasma IL-18 was significantly higher in patients with severe ulcerative colitis (535±115 pg/mL) than in patients with mild ulcerative colitis (195±41 pg/mL), and in healthy controls. Although the mucosal mean IL-18 concentration in severe ulcerative colitis (2 523±618 pg/mg protein) doubled values observed in mild one (1347±308 pg/mg protein), there was no statistically significant difference. CONCLUSION: Plasma IL-18 can be considered as a surrogate marker helpful in evaluation of ulcerative colitis activity.
文摘Objective:To investigate the effect of interleukin-18 (IL-18) on immune response induced by plasmid encoding hepatitis B virus middle protein antigen and to explore new strategies for prophylactic and therapeutic HBV DNA vaccines.Methods:BALB/c mice were immunized with pCMV-M alone or co-immunized with pcDNA3-18 and pCMV-M and then their sera were collected for analysing anti-HBsAg antibody by ELISA;splenocytes were isolated for detecting specific CTL response and cytokine assay in vitro.Results:The anti-HBs antibody level of mice co-immunized with pcDNA3-18 and pCMV-M was slightly higher than that of mice immunized with pCMV-M alone,but there was not significantly different (P>0.05).Compared with mice injected with pCMV-M, the specific CTL cytotoxity activity of mice immunized with pcDNA3-18 and pCMV-M was significantly enhanced (P<0.05) and the level of IFN-γ in supernatant of splenocytes cultured with HBsAg in vitro was significantly elevated (P<0.05) while the level of IL-4 had no significant difference (P>0.05).Conclusion:The plasmid encoding IL-18 together with HBV M gene DNA vaccines may enhance specific TH1 cells and CTL cellular immune response induced in mice, so that IL-18 is a promising immune adjuvant.
基金Supported by The National Natural Science Foundation of China,No.30771032 and No.30700879the National 973 Program of China,No.2006CB503900+1 种基金the National 863 Program of China,No.2006AA02A112the Natural Science Foundation of Beijing City,No.7062067
文摘AIM:To investigate the effects of rosiglitazone(RGZ) on expression of interleukin-18(IL-18) and caspase-1 in liver of non-alcoholic fatty liver disease(NAFLD) rats.METHODS:Twenty-eight Sprague-Dawley(SD) rats were randomly divided into control,NAFLD,and RGZ treated NAFLD groups.A NAFLD rat model of NAFLD was established by feeding the animals with a high-fat diet for 12 wk.The NAFLD animals were treated with RGZ or vehicle for the last 4 wk(week 9-12) and then sacrificed to obtain liver tissues.Histological changes were analyzed with HE,oil red O and Masson's trichrome staining.Expressions of IL-18 and caspase-1 were detected using immunohistochemical staining and semi-quantitative reverse-transcription polymerase chain reaction(RT-PCR) analysis.RESULTS:The expression levels of both IL-18 and caspase-1 were higher in the liver of NAFLD group than in the control group.Steatosis,inflammation and fibrosis,found in the liver of NAFLD rats,were significantly improved 4 wk after RGZ treatment.The elevated hepatic IL-18 and caspase-1 expressions in NAFLD group were also significantly attenuated after RGZ treatment.CONCLUSION:RGZ treatment can ameliorate increased hepatic IL-18 production and histological changes in liver of NAFLD rats.The beneficial effects of RGZ on NAFLD may be partly due to its inhibitory effect on hepatic IL-18 production.
文摘Objective： To investigate the relationship between serum interleukin-18 and interleukin-12 levels and clinicopathology of renal cell carcinoma. Methods： Peripheral blood samples were obtained from 20 healthy volunteers and 60 patients with renal cell carcinoma before curative surgery. IL-12 and IL-18 levels were determined by enzyme-linked immunosorbent assay. Results： Mean serum IL-12 and IL-18 levels were significantly higher in patients with renal cell carcinoma compared with healthy volunteers （P〈0.05） and mean serum IL-12 and IL-18 levels increased in patients as the pathologic stage progressed. A positive correlation was observed between serum IL-12 and IL-18 levels （P〈0.05）. In patients with renal cell carcinoma, increasing serum IL-12 and IL-18 levels correlated with pathological stage and Fuhrman grade. Conclusion： Serum IL-12 and IL-18 might be useful tumor markers in patients with renal cell carcinoma.
基金supported by the Natural Science Foundation of Fujian Province (No. 2006J0342)Scholastic Development Foundation of Fujian Medical University (No. JS07006)
文摘Objective： To investigate the effects of interleukin-18 （IL-18） on implanted Lewis lung cancer in suppressing angiogenesis and lymphangiogenesis. Methods： One week after hypodermic inoculation of Lewis cells, sixteen tumor-bearing syngeneic mice were randomly divided into two groups. The mice in the treatment group （group A） were intraperitoneally injected with the IL-18 and in the control group （group B） were intraperitoneally injected with normal saline for 7 days. The mice were killed on day 19. The morphology of the tumors was studied, the growth curve was described and the tumor inhibition rate was calculated. The numbers of metastasized pulmonary colonies were calculated using hematoxylin-eosin （HE） staining. The vascular endothelial growth factor A （VEGF-A）, vascular endothelial growth factor C （VEGF-C）, microvessel density （MVD） and lymphatic microvessel density （LMVD） in tumor mass were measured by immunohistochemistry staining （IHCS）. Results： In the group A, the tumor volume, tumor weigh, lung metastatic nodules, expression of VEGF-A and VEGF-C, MVD were all decreased significantly （P0.01 or P0.05）. The tumor inhibition rate was 75% and the inhibition rate of lung metastatic nodules was 61%. The LMVD in group A was also lower than group B, but without significant difference （P0.05）. Conclusion： IL-18 could suppress the tumor growth and metastasis of implanted Lewis lung cancer by way of down-regulating VEGF-A and VEGF-C expression, suppressing angiogenesis and lymphangiogenesis.
文摘AIMTo assess circulatory levels of interleukin-18 (IL-18) and determine whether the presence of IL-18 promoter polymorphism influences metabolic syndrome phenotypes. METHODSThis study recruited one hundred and eighty individuals divided into three groups with sixty subjects each as: Normal weight (18.0-22.9 kg/m<sup>2</sup>), overweight (23.0-25.9 kg/m<sup>2</sup>) and obese (> 26.0 kg/m<sup>2</sup>) according to South Asian criteria of BMI. Fasting blood glucose (FBG), Lipid profile, insulin, IL-18 and tumor necrosis factor (TNF)α were measured using ELISA kits, whereas low density lipoprotein (LDL)-cholesterol, insulin resistance (HOMA-IR) and insulin sensitivity (QUICKI) were calculated. The body fat percentage (BF) was measured through bioelectrical impedance analysis; waist and hip circumference were measured. Genotyping of IL-18 -607 C/A polymorphism was performed by using tetra-primer amplification refractory mutation system. Student t test, One-way analysis of variance, Hardy-Weinberg equilibrium, Pearson’s χ<sup>2</sup> test and Pearson’s correlation were used, where a P value < 0.05 was considered significant. RESULTSIn an aged matched study, obese subjects showed higher levels of FBG, cholesterol, triglycerides and LDL levels as compared to normal weight (P < 0.001). Highest levels of IL-18 and TNF levels were also seen in obese subjects (IL-18: 58.87 ± 8.59 ng/L) (TNF: 4581.93 ± 2132.05 pg/mL). The percentage of IL-18 -607 A/A polymorphism was higher in overweight and obese subjects vs normal weight subjects (P < 0.001). Moreover, subjects with AA genotype had a higher BF, insulin resistance, TNFα and IL-18 levels when compared with subjects with AC (heterozygous) or CC (wild type) genotypes. However, we did not find any difference in the lipid profile between three subgroups. CONCLUSIONThis preliminary data suggests that IL-18 polymorphism affects IL-18 levels that might cause low grade inflammation, further exacerbated by increased TNFα. All these increase the susceptibility to develop MetS. Further studies are required to validate our findings.
基金Supported by the grants of the Natural Science Foundation Program of Fujian Province (No. 2006J0342)the Scholastic Development Foundation of Fujian Medical University (No. JS07006)
文摘Objective： The aim of our study was to investigate the effects of interleukin-18 （IL-18） on implanted Lewis lung cancer in suppressing tumor growth and inducing tumor cells apoptosis. Methods： One week after hypodermic inoculation of Lewis cells, sixteen tumor-bearing syngeneic mice were randomly divided into two groups. The mice in the treatment group were intrapedtoneal injected with the IL-18, in the control group were intrapedtoneal injected with normal saline. The health conditions of the mice were measured, the morphology of the tumors was studied and the apoptosis of implanted lung cancer cells was detected by TUNEL to evaluated the effects of IL-18. Results： IL-18 had no significant effects on the health condi- tions of the mice, but it could suppress the implanted tumor growth （inhibition rate was 75%） and induce tumor cells apoptosis. Conclusion： IL-18 can suppress the implanted Lewis lung cancer cells by way of inducing tumor cells apoptosis. It could be used as a new strategy for lung cancer.
基金supported by the National Natural Science Foundation of China,No.81260296(to LJA)and 81300987(to QLi)
文摘Exposure to maternal stress during prenatal life is associated with an increased risk of neuropsychiatric disorders, such as depression and anxiety, in offspring. It has also been increasingly observed that prenatal stress alters the phenotype of offspring via immunological mechanisms and that immunological dysfunction, such as elevated interleukin-18 levels, has been reported in cultures of microglia. Prenatal restraint stress(PRS) in rats permits direct experimental investigation of the link between prenatal stress and adverse outcomes. However, the majority of studies have focused on the consequences of PRS delivered in the second half of pregnancy, while the effects of early prenatal stress have rarely been examined. Therefore, pregnant rats were subjected to PRS during early/middle and late gestation(days 8–14 and 15–21, respectively). PRS comprised restraint in a round plastic transparent cylinder under bright light(6500 lx) three times per day for 45 minutes. Differences in interleukin-18 expression in the hippocampus and in behavior were compared between offspring rats and control rats on postnatal day 75. We found that adult male offspring exposed to PRS during their late prenatal periods had higher levels of anxiety-related behavior and depression than control rats, and both male and female offspring exhibited higher levels of depression-related behavior, impaired recognition memory and diminished exploration of novel objects. Moreover, an elevated level of interleukin-18 was observed in the dorsal and ventral hippocampus of male and female early-and late-PRS offspring rats. The results indicate that PRS can cause anxiety and depression-related behaviors in adult offspring and affect the expression of interleukin-18 in the hippocampus. Thus, behavior and the molecular biology of the brain are affected by the timing of PRS exposure and the sex of the offspring. All experiments were approved by the Animal Experimentation Ethics Committee at Kunming Medical University, China(approval No. KMMU2019074) in January 2019.
文摘Interleukin-18(IL-18) is a cytokine with many functions. This study was to investigate the serum levels of IL-18 and their clinical significance in patients with colore3ctaql carcinomas. Methods: Peripheral blood samples were obtained from 106 patients with colorectal carcinoma and 60 volunteers. The serum IL-18 levels were determined in each sample with an enzyme-linked immunosorbent assay (ELISA). Results: In patients before 1997, the mean IL-18 level was 338.46 pg/ml; in patients after 1997, the mean IL-18 level was 328.85 pg/ml, there is no evidence of loss of IL-18 immunoreactivity after prolonged storage at -80℃. The mean serum IL-18 level in 106 patients with colorectal carcinoma was significantly higher compared with the 60 healthy volunteers (P<0.05). Although the IL-18 level in patients with stage I did not differ from controls, the serum IL-18 levels of patients with stage II, stage III and stage IV disease were significantly higher compared with healthy control (P<0.05). The mean serum IL-18 level of patients with stage III disease, while the difference between patients with stage II and stage IV was not statistically significant (P>0.05). The survival rate of patients with IL-18 levels ≥346 pg/ml (n=47 patients) was significantly worse compared with patients who had IL-18 levels <346 pg/ml(n=57 patients). The 5-year-survival rates were 5.3% and 18.6%, respectively. Multivariate analysis using a Cox proportional hazards model identified the serum IL-18 level as an independent prognostic factor for survival Conclusion: The serum IL-18 level has a significant correlation with survival curve. The serum IL-18 level may represent a significant postoperative prognostic determinant in patients with colorectal carcinoma.
文摘Objective: To investigate the effect of interleukin-12 (IL-12) and interleukin-18 (IL-18)DNA immunization on immune response induced by HIV-1 DNA vaccine and to explore new strategies for therapeutic HIV DNA vaccine. Methods: The recombinant expression vector pCI-neoGAG was constructed by inserting HIV Gag gene into the eukaryotic expression vector pCI-neo. Balb/c mice were immunized with pCI-neoGAG alone or co-immunized with the DNA encoding for IL-12 or IL-18.Anti-HIV antibody and IFN-γ were tested by ELISA,and splenocytes were isolated for detecting antigen-specific lymphoproliferative responses and specific CTL response by MTT assay and LDH assay respectively. Results: The anti-HIV antibody titers of mice co-immunized with pCI-neoGAG and the DNA encoding for IL-12 or IL-18 were lower than that of mice immunized with pCI-neoGAG alone(P<0.01). In contrast, the IFN-γ level of mice co-immunized with pCI-neoGAG and the DNA encoding for IL-12 or IL-18 was higher than that of mice immunized with pCI-neoGAG alone (P<0.01).Furthermore, compared with mice injected with pCI-neoGAG alone, the specific CTL cytotoxity activity and antigen-specific lymphoproliferative responses of mice immunized with pCI-neoGAG and the DNA encoding for IL-12 or IL-18 were significantly enhanced respectively (P<0.01). Conclusion: The DNA encoding for IL-12 or IL-18 together with HIV DNA vaccine may enhance specific Th-1 responses and cellular immune response elicited in mice. Hence, the DNA encoding for IL-12 or IL-18 are promising immune adjuvants for HIV-1 DNA vaccine.
