Bacterial Peptides Enhance Inflammatory Activity in a Rat Model of Colitis

Bacterial products released within the gut lumen may alter the course of inflammatory bowel lesions. The effect of intraluminal N-formyl methionyl-leucyl-phenylalanine on mucosal release of inflammatory mediators was investigated in normal and colitis rats (at 1 and 7 days after induction of colitis by trinitrobenzenesulfonic acid). Under anesthesia, the distal colon was perfused using an isosmotic solution with or without synthetic N-formyl methio-nyl-leucyl-phenylalanine (100 nmol/ml). Effluents were assayed for eicosanoid (PGE2, TXB2 and LTB4) concentration. Myeloperoxidase activity was measured in colonic wall homogenates. In normal rats, peptide perfusion did not change mucosal release of PGE2, TXB2 and LTB4. Colitic rats showed high baseline release of eicosanoids. The peptide did not further increase PGE2 and TXB2 release, but significantly stimulated LTB4 both on days 1 and 7 after induction of colitis. Rats with high myeloperoxidase activity in the colonic wall showed a marked LTB4 response to the peptide. Finally, peptide perfusion increased tissue myeloperoxidase activity in colitis at day 7 but not in colitis at day 1 or in normal rats. In conclusion, bacterial products may activate inflammation. This mechanism of lumen-wall interaction might be involved in the perpetuation of inflammatory lesions of the colonic mucosa.