ALPHA-MSH MODULATES EXPERIMENTAL INFLAMMATORY BOWEL-DISEASE

The mechanisms underlying inflammatory bowel disease (IBD) remain obsc ure but the importance of inflammatory processes is clear and most pha rmacological therapies inhibit inflammation. The search for more effec tive agents with low toxicity continues. To test the possibility that the antiinflammatory/anticytokine peptide alpha-MSH can be used to con trol 1BD, the peptide was administered to a murine colitis model. The peptide treatment had marked salutary effects: it reduced the appearan ce of fecal blood by over 80%, inhibited weight loss, and prevented di sintegration of the general condition of the animals. Mice given alpha -MSH showed markedly lower production of TNF alpha by tissues of the l ower colon stimulated with concanavalin A; the inhibitory effect of al pha-MSH on production of inflammatory nitric oxide by lower bowel tiss ue was even greater. The combined results indicate that alpha-MSH modu lates experimental IBD, perhaps by inhibiting production within the gu t of the local proinflammatory agents TNF alpha and nitric oxide, or b y inhibiting inflammatory processes closely linked to these mediators. (C) 1997 Elsevier Science Inc.