In chronic colitis exacerbation of altered motility induced by the bacterial peptide formyl‐Methionyl‐Leucyl‐Phenylalanine (fMLP) is associated with dysregulation of the immune system

Abstract

The pathophysiological role of bacterial peptides in the symptoms associated with colitis is unclear.Aim:To investigate the role of fMLP in chronic colitis.Methods:Colitis was induced in rats by administration of trinitrobenzene sulfonic acid (TNBS; 30mg in 50% ETOH ic). Chronic relapsed inflammation was induced 6 weeks later by TNBS (5mg/kg iv), with or without the bacterial peptide (1.0mM in 6% DMSO iv) at 24 hour time intervals over three days. The colons were assessed for macroscopic and microscopic damage, and immunohistochemistry. Tissue cytokine levels were measured by ELISA and real‐time RT‐PCR. Segments of longitudinal and circular smooth muscle from proximal and distal colon were mounted in tissue baths for isometric recording in response to Ach.Results:Administration of fMLP exacerbated both macroscopic and microscopic damage (p<0.05). Cellular infiltration and increased numbers of T‐cells and dendritic cells were found. These animals had more diarrhea and increased muscle tension in response to Ach. Levels of IFNγ and TNFα increased after administration of fMLP (p<0.05), while IL‐10 levels were decreased (p<0.05), with little change in TGFβ or IL‐18.Conclusions:Components of the intestinal microflora may drive a dysregulation of the immune system and influence the contractile responses of the colon in chronic colitis contributing to the symptoms observed in patients. NCRR/RCMI 2G12RR03050