Inflammatory bowel diseases are chronic inflammatory disorders of the gastrointestinal tract.
Vasoactive intestinal peptide (VIP) is a
neuropeptide with known anti-inflammatory activity. We have demonstrated previously that administration of VIP inhibits leucocyte migration in a murine model of delayed-type
hypersensitivity, and anti-inflammatory efficacy is supported by other studies. The aim of this study was to investigate the VIP effects in a murine model of intestinal
inflammation.
Colitis was induced in BALB/c mice by a 2.5 mg
enema of 2,4,6-trinitrobenzenesulphonic
acid (TNBS) and the mice were killed on day 7. Mice were administered either a 3-day (therapeutic) or 7-day (prophylactic) constant infusion of VIP by subcutaneously implanted mini-osmotic pumps, or intraperitoneal (i.p.) injection of VIP on alternate days over 7 days. Clinical disease scores, weight changes, histopathology of colon tissues, plasma VIP levels,
cytokine levels and chemotaxis of peripheral blood mononuclear cells were evaluated. After administration of TNBS, mice quickly developed severe
colitis accompanied by dramatic
body weight loss (20% by day 6) and high mortality (30%). Prophylactic treatment using high-dose VIP abrogated leucocyte chemotaxis; however, it failed to ameliorate the
weight loss and mortality. Moreover, VIP delivered either by constant infusion or i.p. failed to modify the clinical, histological or
cytokine markers of disease. Our studies show that, despite an ability to inhibit
chemokine-induced chemotaxis of mononuclear cells, VIP was unable to modulate TNBS-induced
colitis. This contrasts with the efficacy of VIP in models of mild inflammatory disease and suggests that VIP is unlikely to provide a useful model for novel anti-IBD
therapy.