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)], alpha-melanocyte-stimulating hormone [alpha-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 alpha in the blood of HIV patients. Cytokine production was measured in whole blood samples stimulated with LPS in the presence or absence of alpha-MSH (1-13), alpha-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), alpha-MSH (1-13) inhibited production of IL-1 beta and TNF alpha 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.
Catania
A
A
Third Division of Internal Medicine, IRCCS Ospedale Maggiore, Milano, Italy. Anna.Catania@unimi.it
Garofalo
L
L
Cutuli
M
M
Gringeri
A
A
Santagostino
E
E
Lipton
J M
JM
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000328:Adult; D003366:Cosyntropin / Q000494:pharmacology; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology; D015658:HIV Infections / Q000097:blood*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000097:blood*; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D000521:alpha-MSH / Q000494:pharmacology*
D015699:HIV Envelope Protein gp120; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D003366:Cosyntropin; D000521:alpha-MSH; D000324:Adrenocorticotropic Hormone