a-Melanocyte-stimulating hormone (a-MSH) is a 13-amino acid peptide hormone produced by post-translational processing of proopiomelanocortin (POMC) in the pituitary gland, as well as in keratinocytes, astrocytes, monocytes, and gastrointestinal cells.{47500} It is an agonist of melanocortin receptor 3 (MC3R) and MC4R that induces cAMP production in Hepa cells expressing the human receptors (EC50s = 0.16 and 56 nM, respectively).{45139} a-MSH (100 pM) reduces S. aureus colony formation and C. albicans germ tube formation in vitro.{55058} It inhibits endotoxin-, ceramide-, TNF-a-, or okadaic acid-induced activation of NF-kB in U937 cells.{47500} a-MSH reduces IL-6- or TNF-a-induced ear edema in mice.{55059} It also prevents the development of adjuvant-induced arthritis in rats and increases survival in a mouse model of septic shock. Increased plasma levels of a-MSH are positively correlated with delayed disease progression and reduced death in patients with HIV.{47500}