Antiinflammatory influences of alpha-MSH molecules: central neurogenic and peripheral actions

Abstract

alpha-Melanocyte-stimulating hormone (alpha-MSH1-13) and its COOH-terminal tripeptide alpha-MSH11-13 (Lys Pro Val) inhibit inflammation when administered systemically. Recent evidence indicates that alpha-MSH1-13 can likewise inhibit inflammation in the skin solely via an action within the brain. Because of the potential importance of this discovery to understanding the control of inflammation and because alpha-MSH molecules might be useful for treatment of inflammation, experiments were performed to learn more about the mechanisms of action of these peptides. In tests on inflammation induced in the mouse ear by intradermal injections of recombinant human interleukin-1 beta, alpha-MSH1-1-13 administered intracerebroventricularly effectively reduced inflammation. This effect of centrally administered alpha-MSH1-13 was inhibited by systemic injection of the nonspecific beta-adrenergic receptor blocker propranolol and by administration of a specific beta 2-adrenergic receptor antagonist; the effect was not altered by blockade of cholinergic, alpha-adrenergic, or beta 1-adrenergic receptors. In mice with inflammation induced in a hind paw and with the spinal cord transected, the antiinflammatory effect of centrally administered alpha-MSH1-13 was prevented, indicating that intact descending neuronal pathways are required for the antiinflammatory influence of the central peptide. Systemic injection of alpha-MSH1-13 in animals with spinal cord transection had a smaller and later antiinflammatory effect, which suggests that the molecule also has an action, albeit lesser, in the periphery. However, alpha-MSH11-13 injected intraperitoneally had marked antiinflammatory activity in animals with spinal cord transection.(ABSTRACT TRUNCATED AT 250 WORDS)

α-MSH Modulates Local and Circulating Tumor Necrosis Factor-α in Experimental Brain Inflammation

“…Central ␣-MSH modulates the increase in circulating TNF-␣ induced by LPS acting solely within the brain Whatever the basis of the increase in circulating TNF-␣, injection of ␣-MSH into the brain reduced it. The dose of ␣-MSH that inhibited circulating TNF-␣ effectively reduced peripheral inflammation after central injection in earlier experiments (Lipton et al, 1991;Ceriani et al, 1994;Macaluso et al, 1994). If circulating TNF-␣ contributes to the inflammatory response in the periphery, central ␣-MSH likely inhibits this inflammation in some part by modulating circulating TNF-␣.…”

Targeting Melanocortin Receptors as a Novel Strategy to Control Inflammation

“…This small peptide shares the anti-inflammatory and antipyretic effects of ␣-MSH (1-13) (Richards and Lipton, 1984b;Hiltz and Lipton, 1989;Mugridge et al, 1991;Hiltz et al, 1992;Poole et al, 1992;Uehara et al, 1992;Watanabe et al, 1993;Ceriani et al, 1994b;Macaluso et al, 1994;Bhardwaj et al, 1996;Ichiyama et al, 1999c;Luger et al, 1999;Haddad et al, 2001;Mandrika et al, 2001). Furthermore, ␣-MSH (11-13) reduced NF-B translocation to the nucleus much as the full-length ␣-MSH Barcellini et al, 2000;Mandrika et al, 2001).…”

The melanocortin receptor type 3 agonistd-Trp(8)-γMSH decreases inflammation and muscle wasting in arthritic rats

“…It is well known that alpha‐melanocyte stimulating hormone (αMSH) is able to decrease inflammation both at central and peripheral levels 16. Blockade of NF‐ k B activation is an important mechanism through which αMSH decreases inflammation in different cell types 17, 18.…”