Interleukin 10 (IL-10) in Susceptibility and Pathogenesis of Irritable Bowel Syndrome (IBS)

Abstract

Purpose: IL-10 is an anti-inflammatory cytokine produced by monocytes and lymphocytes that influences immunoregulation and inflammation. In our previous studies we found an association between presence of AA polymorphism in the -1082 IL-10 allele (SNP) and reduced frequency of IBS in a large general medical population. Methods: We investigated the association of this SNP on type of IBS, postinfectious (PI) or idiopathic (I) compared with healthy controls and measured levels of fecal IL-10 in fecal samples in the populations under study. We enrolled 50 subjects with PI-IBS, 50 with I-IBS and 52 healthy subjects as controls. Subjects with either form of IBS completed a validated questionnaire establishing the diagnosis of IBS by Rome II criteria. The subjects provided blood and stool samples. DNA was extracted from blood and subjected to PCR amplification with primers specific for IL-10 with the AA, AT and TT SNPs in -1082 position identified by pyrosequencing. Stool samples were assayed for fecal IL-10 levels by ELISA with quantity correlated with presence of IL-10 genotype. Results: AA SNP was seen in 20 (40%) with PI-IBS, 16 (32%) with I-IBS, 36 (35%) for both IBS groups combined compared with 28 (52%) of controls (p = 0.037 for all IBS subjects vs. controls). The median concentrations of IL-10 in stools (pg/mL) for the four respective groups were: 2.78, 2.59, 1.85 and 5.79 (p = 0.023 for all IBS groups vs. controls). The two IBS groups did not differ in the frequency of SNP or fecal concentration of IL-10. Conclusion: Reduced frequency of AA SNP in the -1082 IL-10 gene and corresponding reductions in fecal levels of IL-10 are seen in both forms of IBS compared with healthy controls and may provide clues as to the pathogenesis of IBS.