CENTRAL NEUROGENIC ANTIINFLAMMATORY ACTION OF ALPHA-MSH - MODULATION OF PERIPHERAL INFLAMMATION-INDUCED BY CYTOKINES AND OTHER MEDIATORS OFINFLAMMATION

The neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) has potent antipyretic and antiinflammatory properties. When administered systemically, the naturally occurring molecule and its COOH-terminal t ripeptide sequence inhibit inflammation induced by peripherally applie d irritants and intradermal injections of mediators of inflammation su ch as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis f actor-alpha (TNF alpha). We recently found that alpha-MSH can act sole ly within the brain to inhibit inflammation caused by a general irrita nt applied to the skin. This activity appears to be shared with salicy late drugs and the combined observations suggest the existence of desc ending neurogenic antiinflammatory signals capable of modulating infla mmation in peripheral tissues. To improve our knowledge of the scope o f this action of the peptide, alpha-MSH was injected into the cerebral ventricles (i.c.v.) of mice that had received intradermal injections in the ear of mediators of inflammation: IL-1 beta, IL-8, leukotriene B-4, and platelet-activating factor. The centrally administered peptid e inhibited the actions of all of these proinflammatory agents as dete rmined from comparisons with measures of ear edema over time in contro l animals; this indicates that the central peptide can alter inflammat ion induced in the periphery by major mediators of inflammation. In te sts confined to IL-1 beta, central administration of alpha-MSH(11-13) was also effective. These findings support the concept of a descending neurogenic antiinflammatory influence promoted by an action of alpha- MSH within the brain, an inhibitory influence that is not restricted t o modulation of just one or a limited set of the mediators of inflamma tion.