Anti-inflammatory effects of the hormone alpha-MSH

This post is about a relatively older but still-interesting line of research linking the human hormone alpha-melanocyte-stimulating hormone (alpha-MSH) to reduction of inflammation.  Melanocytes are cells which produce the pigment melanin which gives color to the skin, eyes and hair.   In the blog post, More research insight on gray hair and adult stem cell reproduction I discussed how declining numbers of melanocyte stem cells is responsible for the hair of older people turning white or gray.  Melanocytes are found in multiple body tissues in addition to hair follicles, including the skin, meninges, bone and heart.  The role of alpha-MSH in activating  activate melanocytes has been extensively studied for some time(ref)(ref)(ref).  Alpha-MSH is produced in the pituitary gland, in neural cells, monocytes and certain types of skin cells.  For example, consider suntan.  When ultraviolet radiation impacts on keratinocytes, the keratinocytes release alpha-MSH.  Melanocytes have target receptors for alpha-MSH and when alpha-MSH binds to skin melanocytes, they generates the black pigment eumelanin.  The result is suntan. [Actually the situation is a bit more complicated than this since other factors are also involved in producing eumelanin and the melanocytes have other regulatory functions besides producing eumelanin(ref)(ref)(ref)(ref).]

With respect to theories of aging it is interesting that Alpha-MSH inhibits the expression of NF-kappaB and is a powerful anti-inflammatory, affecting what is possibly a key pathway in inflammatory pathologies(ref). “We report that alpha-melanocyte-stimulating hormone(10–9 M) was effective in opposing a tumor necrosis factor- stimulated increase in NF- B DNA binding activity in: (i) normal ocular melanocytes; (ii) cells cultured from ocular melanoma tumors; and (iii) two cutaneous melanoma cell lines(ref).”

  This is quite interesting since runaway expression on NF-kappaB and TNF-alpha seem to be characteristic of melanoma.  Systemic administration of alpha-MSH appears to inhibit inflammation in general.  For example, it has been shown to be capable of inhibiting colonic inflammation in inflammatory bowel disease, at least in rats(ref).  It can inhibit edema in the mouse paw and acute ear inflammation in mice(ref). Another study description indicates “The results suggest that anti-inflammatory influences of neural origin that are triggered by alpha-MSH could be used to treat systemic inflammation. In addition to its central influences, alpha-MSH has inhibitory effects on peripheral host cells, in which it reduces release of pro-inflammatory mediators. Alpha-MSH reduces chemotaxis of human neutrophils and production of TNF-alpha, neopterin, and NO by monocytes. In research on septic patients, alpha-MSH inhibited release of TNF-alpha, interleukin-1 beta (IL-1 beta), and interleukin-8 (IL-8) in whole blood samples in vitro(ref).”  In the nervous system, the anti-inflammatory effects of alpha-MSH are communicated via neurogenic signaling.  One report indicates “We recently found that alpha-MSH can act solely within the brain to inhibit inflammation caused by a general irritant applied to the skin. This activity appears to be shared with salicylate drugs and the combined observations suggest the existence of descending neurogenic anti-inflammatory signals capable of modulating inflammation in peripheral tissues(ref).”The way that alpha-MSH works to limit inflammation appears to be through inhibiting expression of NF-kappaB which is essential for the expression of proinflammatory cytokines.  It appears to do this by prevention of degradation of IkappaBalpha, a protein that keeps NF-kappaB locked up in the cell cytoplasm and out of the nucleus(ref). 

NF-kappaB plays a central role in the Programmed Epigenomic Changes theory of aging.  There does not seem to be much current research action on the anti-inflammatory effects alpha-MSH or use of alpha-MSH as an anti-inflammatory therapy but I would not be surprised to see this thread picked up again at some point in an expanded context.