Melanocortin peptide therapy for the treatment of arthritic pathologies.
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 [alpha-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 alpha-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.
Getting
S J
SJ
Inflammation and Infection Group, School of Life Sciences, University of Westminster, London. s.getting@wmin.ac.uk
Kaneva
M
M
Bhadresa
Y
Y
Renshaw
D
D
Leoni
Giovanna
G
Patel
H B
HB
Kerrigan
M J P
MJ
Locke
I C
IC
D000818:Animals; D001168:Arthritis / Q000188:drug therapy*; D015210:Arthritis, Gouty / Q000188:drug therapy; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D053486:Melanocortins / Q000627:therapeutic use*; D010003:Osteoarthritis / Q000188:drug therapy; D044101:Receptors, Melanocortin / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
D053486:Melanocortins; D044101:Receptors, Melanocortin