Endotoxin causes release of ɑ-melanocyte-stimulating hormone in normal human subjects

The neuropeptide ɑ-melanocyte stimulating hormone (ɑ-MSH), a proopiomelanocortin derivative, is a potent modulator of fever, inflammation, and other aspects of the acute-phase response. ɑ-MSH concentrations increase in rabbit plasma after large doses of endotoxin, but it is not known if changes in this potent peptide likewise occur during endotoxemia in humans. The current study was performed to assess changes in plasma ɑ-MSH during the acute inflammatory response to endotoxin in normal humans. ɑ-MSH was measured in plasma samples obtained over a 5-hour study period in 20 normal human subjects given endotoxin. Plasma adrenocorticotropic hormone (ACTH) and tumor necrosis factor were also measured at the same time points. Endotoxin administration caused fever-related increases in plasma ɑ-MSH. Five subjects with a high thermal response to endotoxin (>2.6°C above baseline) showed a 2- to 4-fold increase in circulating ɑ-MSH whereas subjects with lower fever (