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TheScientificWorldJOURNAL
Volume 9 (2009), Pages 1394-1414
http://dx.doi.org/10.1100/tsw.2009.163
Review Article

Melanocortin Peptide Therapy for the Treatment of Arthritic Pathologies

1Inflammation and Infection Group, School of Life Sciences, University of Westminster, London, UK
2Centre for Biochemical Pharmacology, William Harvey Research Institute, London, UK

Received 3 September 2009; Revised 3 December 2009; Accepted 4 December 2009

Academic Editor: Mauro Perretti

Copyright © 2009 S. J. Getting et al.

Abstract

Arthritic pathologies are a major cause of morbidity within the western world, with rheumatoid arthritis affecting approximately 1% of adults. This review highlights the therapeutic potential of naturally occurring hormones and their peptides, in both arthritic models of disease and patients. The arthritides represent a group of closely related pathologies in which cytokines, joint destruction, and leukocytes play a causal role. Here we discuss the role of naturally occurring pro-opiomelanocortin (POMC)-derived melanocortin peptides (e.g., alpha melanocyte stimulating hormone [a-MSH]) and synthetic derivatives in these diseases. Melanocortins exhibit their biological efficacy by modulating proinflammatory cytokines and subsequent leukocyte extravasation. Their biological effects are mediated via seven transmembrane G-protein-coupled receptors, of which five have been cloned, identified, and termed MC1 to MC5. Adrenocorticotrophic hormone represents the parent molecule of the melanocortins; the first 13 amino acids of which (termed a-MSH) have been shown to be the most pharmacologically active region of the parent hormone. The melanocortin peptides have been shown to display potent anti-inflammatory effects in both animal models of disease and patients. The potential anti-inflammatory role for endogenous peptides in arthritic pathologies is in its infancy. The ability to inhibit leukocyte migration, release of cytokines, and induction of anti-inflammatory proteins appears to play an important role in affording protection in arthritic injury, and thus may lead to potential therapeutic targets.