Antimicrobial effects of α‐MSH peptides

The presence of the ancient antiinflammatory peptide α‐melanocyte‐stimulating hormone [α‐MSH (1–13), SYSMEHFRWGKPV] in barrier organs such as gut and skin suggests a role in the nonspecific (innate) host defense. α‐MSH and and its carboxy‐terminal tripeptide (11–13, KPV) were determined to have antimicrobial influences against two major and representative pathogens: Staphylococcus aureus and Candida albicans. α‐MSH peptides significantly inhibited S. aureus colony formation and reversed the enhancing effect of urokinase on colony formation. Antimicrobial effects occurred over a broad range of concentrations including the physiological (picomolar) range. Small concentrations of α‐MSH peptides likewise reduced viability and germ tube formation of the yeast C. albicans. Antimicrobial influences of α‐MSH peptides could be mediated by their capacity to increase cellular cAMP. Indeed, this messenger was significantly augmented in peptide‐treated yeast and the potent adenylyl cyclase inhibitor dideoxyadenosine (ddAdo) partly reversed the killing activity of α‐MSH peptides. Reduced killing of pathogens is a detrimental consequence of therapy with anti‐inflammatory drugs. Because α‐MSH has potent anti‐inflammatory effects we determined influences of α‐MSH on C. albicans and S. aureus killing by human neutrophils. α‐MSH peptides did not reduce killing but rather enhanced it, likely as a consequence of the direct antimicrobial activity. α‐MSH peptides that combine antipyretic, antiinflammatory, and antimicrobial effects could be useful in treatment of disorders in which infection and inflammation coexist. J. Leukoc. Biol. 67:233–239; 2000.