Comment; α-Melanocyte Stimulating Hormone (αMSH) have not been thought of as host defense effector molecules, natural antimicrobials.  Being produced since primordial/Paleozoic time by barrier epithelial cells make it a “natural” for defense, the fact that it was also in the evolving central nervous system would also make sense as a defense.  Cyclic Adenosine Monophosphate (cAMP) is a well-known intracellular messenger, G-protein-inked melanocortin receptors activating adenylyl cyclase to increase cAMP was known when I tried.  It’s not surprising that it has a role with MSH.  Having practiced medicine for 3 decades, this information was not known when I was educated.  It’s a relatively recent discovery which may provide new ways to fight infections, as a new pathway to microbiocidal activity.

ScientificWorldJournal. 2006 Oct 2;6:1241-6.

Catania A1, Colombo G, Rossi C, Carlin A, Sordi A, Lonati C, Turcatti F, Leonardi P, Grieco P, Gatti S.


The natural antimicrobial peptides are ancient host defense effector molecules, present in organisms across the evolutionary spectrum. Several properties of alpha-melanocyte stimulating hormone (alpha-MSH) suggested that it could be a natural antimicrobial peptide. Alpha-MSH is a primordial peptide that appeared during the Paleozoic era, long before adaptive immunity developed and, like natural antimicrobial molecules, is produced by barrier epithelia, immunocytes, and within the central nervous system. alpha-MSH was discovered to have antimicrobial activity against two representative pathogens, Staphylococcus aureus and Candida albicans. The candidacidal influences of alpha-MSH appeared to be mediated by increases in cell cyclic adenosine monophosphate (cAMP). The cAMP-inducing capacity of alpha-MSH likely interferes with the yeast’s own regulatory mechanisms of this essential signaling pathway. It is remarkable that this mechanism of action in yeast mimics the influences of alpha-MSH in mammalian cells in which the peptide binds to G-protein-linked melanocortin receptors, activates adenylyl cyclase, and increases cAMP. When considering that most of the natural antimicrobial peptides enhance the local inflammatory reaction, the anti-inflammatory and antipyretic effects of alpha-MSH confer unique properties to this molecule relative to other natural antimicrobial molecules. Synthetic derivatives, chemically stable and resistant to enzymatic degradation, could form the basis for novel therapies that combine anti-inflammatory and antimicrobial properties.

Dr. Raymond Oenbrink
Latest posts by Dr. Raymond Oenbrink (see all)