alpha-Melanocyte stimulating hormone (alpha-MSH 1-13) has marked antipyretic effects when administered centrally or peripherally in small doses. A C-terminal fragment, alpha-MSH (11-13), contains an antipyretic message sequence of alpha-MSH; however, the lesser potency of this fragment relative to that of the entire molecule suggests that other amino acids of the alpha-MSH sequence are essential for the full antipyretic effect. Graded doses of alpha-MSH (11-13) (Ac LysProVal NH2), alpha-MSH (10-13) (Ac GlyLysProVal NH2), and alpha-MSH (8-13) (Ac ArgTrpGlyLysProVal NH2), were injected into the cerebral ventricles of rabbits made febrile by IV administration of crude interleukin-1. All three fragments reduced fever in a dose-related manner. The (8-13) sequence was much more effective than the other two fragments, and the (10-13) portion was less effective than the (11-13) tripeptide. None of the fragments was as potent as alpha-MSH (1-13). The results confirm that an antipyretic message resides within alpha-MSH (11-13) and sequential addition of amino acids to alpha-MSH (11-13) can both enhance and reduce the potency of the fragment.

Animals↗

PubMedDate not supplied

Repeated central administration of alpha-MSH does not alter the antipyretic effect of alpha-MSH in young and aged rabbits.

alpha-Melanocyte-stimulating hormone is a potent antipyretic when administered centrally or peripherally; however, there are no previous data on development of tolerance to the antipyretic action of this neuropeptide. In previous research, aged rabbits were more sensitive to low doses of alpha-MSH than young rabbits. We tested the antipyretic action of alpha-MSH in young and old rabbits after twice daily injections of the peptide for 10 days. Neither aged nor younger rabbits showed altered responses to alpha-MSH. This lack of tolerance underscores the importance of alpha-MSH to physiological control and survival of the host.

Aging↗

PubMedDate not supplied

Neuropeptide alpha-MSH antagonizes IL-6- and TNF-induced fever.

The pro-opiomelanocortin-derived peptide melanocyte stimulating hormone (alpha-MSH) antagonizes the fever induced by several stimuli including endotoxin, endogenous pyrogen, and certain cytokines. To determine if alpha-MSH can antagonize the pyrogenic action of recombinant IL-6 and TNF directly within the central nervous system, the cytokines were injected with and without alpha-MSH (200 ng) into a lateral cerebral ventricle of rabbits and rectal temperature was monitored continuously. Central administration of both cytokines caused fever. However, when alpha-MSH was injected after cytokine administration, the fevers were markedly reduced. The results are consistent with previous observations on the antipyretic effect of alpha-MSH and they show that the peptide can act within the brain to antagonize pyrogenic actions of specific cytokines believed to be important in CNS mediation of fever.

Animals↗

PubMedDate not supplied

Double-outlet right ventricle.

Explore the source record for details and available documents.

Aorta, Thoracic↗