The neuroimmunomodulatory peptide α-MSH

Alpha-melanocyte-stimulating hormone (α-MSH), a neuroimmunomodulatory peptide of ancient origin, is known to be involved in the control of host responses. In inflammatory cells, in the periphery and within the central nervous system, α-MSH modulates the production and action of proinflammatory cytokines. This broad influence occurs via endogenous α-MSH (melanocortin) receptors. The key to this anti-inflammatory influence is inhibition of NF-κB. Indeed α-MSH inhibits activation of this nuclear factor through preservation of IκBα, which binds to NF-κB and prevents its migration to the nucleus. Cells transfected with α-MSH plasmid vector are resistant to challenge with bacterial lipopolysaccharide. The peptide also act on central melanocortin receptors to modulate inflammation in the periphery. In brief, α-MSH and certain of its fragments such as α-MSH [11-13] KPV modulate inflammation via three general actions: direct actions on peripheral host cells; actions on inflammatory cells within the brain to modulate local reactions; and descending neural anti-inflammatory pathways that control inflammation in peripheral tissues.