AIM： To investigate interleukin-18 （IL-18） in patients with chronic panreatitis （CP）. METHODS： We studied 29 patients with CP and 30 healthy controls. Peripheral blood mononuclear cells （PBMC） were isolated an...AIM： To investigate interleukin-18 （IL-18） in patients with chronic panreatitis （CP）. METHODS： We studied 29 patients with CP and 30 healthy controls. Peripheral blood mononuclear cells （PBMC） were isolated and incubated with 50 mmol/L ethanol, lipopolysaccharide （LPS） （doses 25 g/L, 250 g/L, 2500 g/L） and both agents for 24 h. Levels of IL-18 in the supernatants, and levels of IL-18, IL-12, interferon （IFN）-T and soluble CD14 in the serum were analysed by EI_ISA technique. Expression of IL-18 in PBMC was investigated by reverse-transcription （RT）-PCR. IL-18 protein levels in CP tissue and in normal pancreas were studied by ELISA technique. IL-18 levels in PBMC and pancreatic tissue were determined by Westernblot. Immunohistochemistry for pancreatic IL-18 expression was performed.RESULTS： In patients, IL-18 serum levels were significantly enhanced by 76% （mean： 289.9 ± 167.7 ng/L） compared with controls （mean： 165.2 ± 43.6 ng/L; P 〈 0.0005）. IL-12 levels were enhanced by 25% in patients （18.3 ± 7.3 ng/L） compared with controls （14.7 ± 6.8 ng/L, P = 0.0576） although not reaching the statistical significance. IFN-γ, and soluble CD14 levels were not increased. In vitro, LPS stimulated significantly and dosedependently IL-18 secretion from PBMC. Incubation with ethanol reduced LPS-stimulated IL-18 secretion by about 50%. The mRNA expression of IL-18 in PBMC and the response of PBMC to ethanol and LPS was similar in CP patients and controls. In PBMC, no significant differences in IL-18 protein levels were detected between patients and controls. IL-18 protein levels were increased in CP tissues compared to normal pancreatic tissues. IL-18 was expressed by pancreatic acinar cells and by infiltrating inflammatory cells within the pancreas. CONCLUSION： IL-18 originates from the chronically inflammed pancreas and appears to be involved in the fibrotic destruction of the organ.展开更多
Objective. There is strong evidence that genetic factors contribute to the susceptibility for inflammatory bowel diseases (IBD). Recently, IL-18 promoter polymorphisms were characterized as risk factors for inflammato...Objective. There is strong evidence that genetic factors contribute to the susceptibility for inflammatory bowel diseases (IBD). Recently, IL-18 promoter polymorphisms were characterized as risk factors for inflammatory diseases such as sepsis, asthma and adult-onset Still’s disease. The aim of this study was to determine whether the -137 (G/C) IL-18 promoter polymorphism was associated with IBD susceptibility. Material and methods. For association analysis, 470 patients with Crohn’s disease (CD), 235 unrelated patients with ulcerative colitis (UC) and 347 controls were enrolled. Furthermore, 233 UC and 470 CD trios were included for segregation analysis. Genotyping was performed by application of the TaqMan MGB biallelic discrimination system. Results. When comparing genotype frequencies of CD and UC patients versus controls, no significant difference was found (p = 0.089 and p =0.078, respectively). However, the Cochran-Armitage trend test revealed a rising probability for CD and UC with increasing number of G alleles (p = 0.030 and 0.028, respectively) for the case-control analysis. On the contrary, the family-based transmission disequilibrium test (TDT) did not show an association of the G allele with CD or UC in 470 CD and 233 UC trios (p = 0.53 and p = 0.79, respectively). Conclusion. The -137 (G/C) IL-18 promoter polymorphism is not a susceptibility factor for IBD in a German cohort.展开更多
基金Supported by a grant to MVS, Forschungsfonds, project number 098200/99-234, Faculty of Clinical Medicine, University of Heidelberg at Mannheim, Germany by a grant "Landesforschungsschwerpunkt-Molekulare Mechanismen alkoholassoziierter Erkrankungen", project number 23-7532, Baden-Württemberg, Germany and by the Dietmar-Hopp-Foundation, Walldorf, Germany
文摘AIM： To investigate interleukin-18 （IL-18） in patients with chronic panreatitis （CP）. METHODS： We studied 29 patients with CP and 30 healthy controls. Peripheral blood mononuclear cells （PBMC） were isolated and incubated with 50 mmol/L ethanol, lipopolysaccharide （LPS） （doses 25 g/L, 250 g/L, 2500 g/L） and both agents for 24 h. Levels of IL-18 in the supernatants, and levels of IL-18, IL-12, interferon （IFN）-T and soluble CD14 in the serum were analysed by EI_ISA technique. Expression of IL-18 in PBMC was investigated by reverse-transcription （RT）-PCR. IL-18 protein levels in CP tissue and in normal pancreas were studied by ELISA technique. IL-18 levels in PBMC and pancreatic tissue were determined by Westernblot. Immunohistochemistry for pancreatic IL-18 expression was performed.RESULTS： In patients, IL-18 serum levels were significantly enhanced by 76% （mean： 289.9 ± 167.7 ng/L） compared with controls （mean： 165.2 ± 43.6 ng/L; P 〈 0.0005）. IL-12 levels were enhanced by 25% in patients （18.3 ± 7.3 ng/L） compared with controls （14.7 ± 6.8 ng/L, P = 0.0576） although not reaching the statistical significance. IFN-γ, and soluble CD14 levels were not increased. In vitro, LPS stimulated significantly and dosedependently IL-18 secretion from PBMC. Incubation with ethanol reduced LPS-stimulated IL-18 secretion by about 50%. The mRNA expression of IL-18 in PBMC and the response of PBMC to ethanol and LPS was similar in CP patients and controls. In PBMC, no significant differences in IL-18 protein levels were detected between patients and controls. IL-18 protein levels were increased in CP tissues compared to normal pancreatic tissues. IL-18 was expressed by pancreatic acinar cells and by infiltrating inflammatory cells within the pancreas. CONCLUSION： IL-18 originates from the chronically inflammed pancreas and appears to be involved in the fibrotic destruction of the organ.
文摘Objective. There is strong evidence that genetic factors contribute to the susceptibility for inflammatory bowel diseases (IBD). Recently, IL-18 promoter polymorphisms were characterized as risk factors for inflammatory diseases such as sepsis, asthma and adult-onset Still’s disease. The aim of this study was to determine whether the -137 (G/C) IL-18 promoter polymorphism was associated with IBD susceptibility. Material and methods. For association analysis, 470 patients with Crohn’s disease (CD), 235 unrelated patients with ulcerative colitis (UC) and 347 controls were enrolled. Furthermore, 233 UC and 470 CD trios were included for segregation analysis. Genotyping was performed by application of the TaqMan MGB biallelic discrimination system. Results. When comparing genotype frequencies of CD and UC patients versus controls, no significant difference was found (p = 0.089 and p =0.078, respectively). However, the Cochran-Armitage trend test revealed a rising probability for CD and UC with increasing number of G alleles (p = 0.030 and 0.028, respectively) for the case-control analysis. On the contrary, the family-based transmission disequilibrium test (TDT) did not show an association of the G allele with CD or UC in 470 CD and 233 UC trios (p = 0.53 and p = 0.79, respectively). Conclusion. The -137 (G/C) IL-18 promoter polymorphism is not a susceptibility factor for IBD in a German cohort.
