Therapeutic effects of vasoactive intestinal peptide in the trinitrobenzene sulfonic acid mice model of Crohn's disease

Background & Aims: Crohn's disease (CD) is a chronic debilitating disease of unknown etiology that is characterized by severe inflammation of the colon. Vasoactive intestinal peptide (VIP) has recently emerged as a promising candidate for treatment of inflammatory Th1-driven diseases. We studied the effect of VIP in trinitrobenzene sulfonic acid (TNBS)-induced colitis, which has clinical and molecular features in common with CD. Methods: A 3-mg enema of TNBS was given to BALB/c mice, and VIP (1 nmol) was given either as a single dose at 12 hours or every other day. Weight loss, histopathology, and chemokine and cytokine levels in serum and colon extracts were assessed. VIP was also tested given 5 days after the onset of TNBS-induced colitis, and its effect was analyzed given a second dose of TNBS. Results: Treatment with VIP reduced the clinical and histopathologic severity of TNBS-induced colitis, abrogating body weight loss, diarrhea, and macroscopic and microscopic intestinal inflammation. The therapeutic effects of VIP were associated with down-regulation of both inflammatory and Th1-driven autoimmune responses, including tumor necrosis factor alpha, interleukin 1, and interleukin 6 in colon extracts and serum as well as interferon gamma by splenic and lamina propria CD4(+) T cells. VIP reduced disease severity when given after disease onset and dramatically reduced disease recurrence given a second dose of TNBS. Conclusions: Our data suggest that VIP has beneficial prophylactic and therapeutic effects in TNBS-induced colitis and is a promising candidate to test for potential benefits in CD.