α-MSH modulates experimental inflammatory bowel disease

The mechanisms underlying inflammatory bowel disease (IBD) remain obscure but the importance of inflammatory processes is clear and most pharmacological therapies inhibit inflammation. The search for more effective agents with low toxicity continues. To test the possibility that the antiinflammatory/anticytokine peptide α-MSH can be used to control IBD, the peptide was administered to a murine colitis model. The peptide treatment had marked salutary effects: it reduced the appearance of fecal blood by over 80%, inhibited weight loss, and prevented disintegration of the general condition of the animals. Mice given α-MSH showed markedly lower production of TNFα by tissues of the lower colon stimulated with concanavalin A; the inhibitory effect of α-MSH on production of inflammatory nitric oxide by lower bowel tissue was even greater. The combined results indicate that α- MSH modulates experimental IBD, perhaps by inhibiting production within the gut of the local proinflammatory agents TNFα and nitric oxide, or by inhibiting inflammatory processes closely linked to these mediators.