The neuropeptide α-MSH has specific receptors on neutrophils and reduces chemotaxis in vitro

The proopiomelanocortin-derived peptide α-melanocyte stimulating hormone (α-MSH) has potent anti-inflammatory effects in all animal models of inflammation against which it has been tested. Understanding of the mechanism by which this occurs is incomplete, although there is recent evidence for α-MSH receptors in murine and human macrophages and for modulation of production of proinflammatory cytokines and related mediators by α-MSH. Because of the prominence of neutrophils in early stages of inflammatory reactions where α-MSH is effective, we examined human neutrophils for evidence of mRNA for α-MSH receptors and for inhibition of neutrophil chemotaxis. There was accumulation of mRNA for melanocortin receptor 1 (MC₁) in RT/PCR product from neutrophils stimulated with interferon and LPS. In subsequent studies α-MSH inhibited migration of neutrophils from most normal volunteers when the cells were placed in FMLP or IL-8 gradients. The inhibition by α-MSH could be traced to alterations in cAMP in neutrophils. The presence of α-MSH receptor message in neutrophils is consistent with the established anti-inflammatory effects of the peptide. Direct inhibition of neutrophil chemotaxis likely contributes to the anti-inflammatory activity of α-MSH.