Antimicrobial effects of alpha-MSH peptides

The presence of the ancient antiinflammatory peptide alpha-melanocyte-stimu lating hormone [alpha-MSH (1-13), SYSMEHFRWGKPV] in barrier organs such as gut and skin suggests a role in the nonspecific (innate) host defense. alph a-MSH and and its carboxy-terminal tripeptide (11-13, KPV) were determined to have antimicrobial influences against two major and representative patho gens: Straphylococcus aureus and Candida albicans. alpha-MSH peptides signi ficantly inhibited S, aureus colony formation and reversed the enhancing ef fect of urokinase on colony formation. Antimicrobial effects occurred over a broad range of concentrations including the physiological (picomolar) ran ge. Small concentrations of alpha-MSH peptides likewise reduced viability a nd germ tube formation of the yeast C. albicans. Antimicrobial influences o f alpha-MSH peptides could be mediated by their capacity to increase cellul ar cAMP, indeed, this messenger was significantly augmented in peptide-trea ted yeast and the potent adenylyl cyclase inhibitor dideoxyadenosine (ddAdo ) partly reversed the killing activity of alpha-MSH peptides. Reduced killi ng of pathogens is a detrimental consequence of therapy with anti-inflammat ory drugs. Because alpha-MSH has potent anti-inflammatory effects we determ ined influences of alpha-MSH on C. albicans and S. aureus killing by human neutrophils. alpha-MSH peptides did not reduce killing but rather enhanced it, likely as a consequence of the direct antimicrobial activity. alpha-MSH peptides that combine antipyretic, anti-inflammatory, anti antimicrobial e ffects could be useful in treatment of disorders in which infection and inf lammation coexist.