Protective role of neurotrophins in experimental inflammation of the rat gut

Background & Aims: Sensory neuropeptides modulate the mucosal response to i nflammation in experimental colitis. Because nerve growth factor (NGF) regu lates the expression of neuropeptides such as substance P and calcitonin ge ne-related peptide (CGRP) and is implicated as a link between the nervous s ystem and the immune system in the inflammatory process, we investigated th e functional role of NGF and neurotrophin-3 during experimental colitis, Me thods: Immunoneutralizing antibodies specific for NGF and neurotrophin (NT) -3 were used to block their endogenous activity. Mild trinitrobenzene sulfo nic acid (TNBS) colitis was induced, and damage scores were assessed after 1 week. Neuropeptide content in the colon and NT messenger RNA (mRNA) expre ssion were determined. Results: The pretreatment with anti-NGF or anti-NT-3 caused a significant 2-3-fold increase in the severity of the experimental inflammation as assessed by a macroscopic damage score, histologic ulcerat ion score, and myeloperoxidase activity in the tissue. CGRP, but not substa nce P, contents in the colon were significantly reduced by NGF immunoneutra lization. NGF mRNA was slightly up-regulated after NGF immunoneutralization , but NT-3 mRNA was unchanged by NT-3 immunoneutralization. CGRP mRNA was n ot significantly changed after 1 week of colitis by NGF or NT-3 immunoneutr alization, whereas beta-preprotachykinin mRNA was up-regulated after immuno neutralization, Conclusions: These findings suggest a regulatory role for N GF and NT-3 in experimental inflammation of the gut. This effect may be par tly caused by the reduction of mucosal CGRP content caused by the NGF block ade.