Melanocortin peptides inhibit production of proinflammatory cytokines in blood of HIV-infected patients

Melanocortins are proopiomelanocortin-derived peptides that include adrenocorticotropic hormone [ACTH (1–39)], α-melanocyte-stimulating hormone [α-MSH (1–13)], and related amino acid sequences. Melanocortin peptides have potent antiinflammatory/anticytokine activity. Because cytokines such as interleukin 1 (IL-1) and tumor necrosis factor (TNF) can be detrimental in HIV-infected patients, we investigated the effects of melanocortins on production of IL-1 and TNF α in the blood of HIV patients. Cytokine production was measured in whole blood samples stimulated with LPS in the presence or absence of α-MSH (1–13), α-MSH (11–13), ACTH (1–24), or ACTH (1–39). Melanocortins reduced production of both cytokines in a concentration-dependent fashion. In separate experiments on normal peripheral blood mononuclear cells (PBMC), α-MSH (1–13) inhibited production of IL-1 β and TNF α induced by HIV envelope glycoprotein gp 120. These results suggest that stimulation of melanocortin receptors in inflammatory cells could be a novel way to reduce production of cytokines that promote HIV replication.