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Neuropeptide alpha-MSH antagonizes IL-6- and TNF-induced fever
L W Martin1, A Catania, M E Hiltz
1Department of Physiology, University of Texas Southwestern Medical Center, Dallas 75235.
Abstract:
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.
Insights
Melanocyte stimulating hormone (alpha-MSH) reduces fevers caused by cytokines within the brain. This peptide acts centrally to antagonize fever, confirming its role in central nervous system fever mediation.
Area of Science:
- Neuroimmunology
- Endocrinology
Background:
- Pro-opiomelanocortin-derived peptides, like alpha-MSH, are known to antagonize fever.
- Cytokines such as IL-6 and TNF are implicated in the central nervous system's mediation of fever.
Purpose of the Study:
- To investigate if alpha-MSH can directly counteract the fever-inducing effects of IL-6 and TNF within the central nervous system.
- To confirm the central antipyretic action of alpha-MSH.
Main Methods:
- Recombinant IL-6 and TNF were administered into the lateral cerebral ventricle of rabbits.
- Alpha-MSH (200 ng) was co-administered with the cytokines.
- Rectal temperature was continuously monitored to assess fever responses.
Main Results:
- Central administration of IL-6 and TNF induced significant fever in rabbits.
- Co-administration of alpha-MSH markedly reduced the fevers caused by these cytokines.
- Alpha-MSH demonstrated a clear antipyretic effect when acting within the brain.
Conclusions:
- Alpha-MSH acts within the central nervous system to antagonize the pyrogenic actions of IL-6 and TNF.
- These findings support the role of alpha-MSH as a key endogenous antipyretic peptide.
- The study confirms the central mechanism by which alpha-MSH modulates cytokine-induced fever.