α-MSH production, receptors, and influence on neopterin in a human monocyte/macrophage cell line

Abstract α-Melanocyte-stimulating hormone (α-MSH), a tridecapeptide derived from pro-opiomelanocortin, has potent antiinflammatory activity in laboratory animals. α-MSH inhibits nitric oxide production by murine macrophages, an influence believed to reflect activation of an autocrine circuit in these cells, one that is based on production and release of α-MSH and subsequent stimulation of melanocortin receptors. We found that THP-1 cells, human monocytic cells, produced α-MSH; this production was increased by interleukin-6, tumor necrosis factor α, or concanavalin A. These cells also expressed the gene for the human α-MSH receptor MC1. Unlike murine macrophages, THP-1 cells produced little nitrite in response to interferon-γ(IFN-γ) and lipopolysaccharide, and a-MSH inhibited this production only slightly. However, production of neopterin, a presumed primate homologue of nitric oxide in lower animals, was increased in THP-1 cells stimulated with IFN-γ plus TNF-α and α-MSH significantly inhibited this production. The evidence indicates that an autocrine regulatory circuit based on α-MSH occurs in human monocyte/macrophages much as in murine macrophages. α-MSH-induced modulation of specific inflammatory mediators/cytotoxic agents appears to differ depending on the importance of the mediators in the myelomonocytic cells of different species.