MELANOCORTIN PEPTIDES INHIBIT PRODUCTION OF PROINFLAMMATORY CYTOKINESIN BLOOD OF HIV-INFECTED PATIENTS

Melanocortins are proopiomelanocortin-derived peptides that include ad renocorticotropic hormone [ACTH (1-39)], alpha-melanocyte-stimulating hormone [alpha-MSH (1-13)], and related amino acid sequences. Melanoco rtin peptides have potent antiinflammatory/anticytokine activity. Beca use 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 (1 in the blood of HIV patients. Cytokine production was measured in whole blood samp les stimulated with LPS in the presence or absence of a-MSH (1-13), (U -MSH (11-13), ACTH (1-24), or ACTH (1-39). Melanocortins reduced produ ction of both cytokines in a concentration-dependent fashion. In separ ate experiments on normal peripheral blood mononuclear cells (PBMC), c r-MSH (1-13) inhibited production of IL-1 beta and TNF alpha induced b y HIV envelope glycoprotein gp 120. These results suggest that stimula tion of melanocortin receptors in inflammatory cells could be a novel way to reduce production of cytokines that promote HIV replication. (C ) 1998 Elsevier Science Inc.