PRO-OPIOMELANOCORTIN-DERIVED PEPTIDES INDUCE IL-10 PRODUCTION IN HUMAN MONOCYTES

There is strong evidence for the existence of a neuroimmune axis which is regulated by a network of interacting cytokines and neuropeptides. Accordingly, pro-opiomelanocortin-derived peptide hormones such as me lanocyte-stimulating hormones (MSH), adrenocorticotropin, and beta-end orphin not only could be detected in many immunocompetent cells but al so turned out to be potent immunomodulating and anti-inflammatory medi ators, mainly through regulating cytokine production, Thus, it was inv estigated whether alpha-MSH, which is known to inhibit immune and infl ammatory responses, would influence the production of the cytokine syn thesis inhibitor IL-10 by human PBMC. Stimulation of PBMC with alpha-M SH resulted in a significantly enhanced release of IL-10 protein, Thes e data were confirmed by Northern blot analysis, which demonstrated in creased IL-10 mRNA expression induced by alpha-MSH. This effect of alp ha-MSH was dose-dependent; maximum IL-10 release and mRNA expression w ere obtained at a concentration of 10(-13) M. There is also clear evid ence that only the C-terminal tripeptide of alpha-MSH was required to enhance IL-10 production, In addition, alpha-MSH and its tripeptide st rongly induced IL-10 in purified monocytes, In contrast, neither unsti mulated nor activated T lymphocytes produced increased amounts of IL-1 0 in response to alpha-MSH. These findings indicate that pro-opiomelan ocortin peptides such as alpha-MSH are able to up-regulate the product ion of suppressor factors such as IL-10 in monocytes and thereby may c ontribute to immunosuppression.