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Abstract:
alpha-MSH reduces fever in rabbits when administered IV, ICV, or by gavage; however, the applicability of this finding to higher species, specifically to primates, has not been determined. In this study, we chose the squirrel monkey as an appropriate primate model since it responds reliably to peripheral administration of bacterial endotoxins that cause fever in man. From pilot studies, doses of S. typhosa endotoxin necessary to produce maximum fever and doses of alpha-MSH which did not cause hypothermia were determined for each animal. In the main experiments endotoxin was given via an indwelling catheter in the saphenous vein, followed by alpha-MSH injections when the rectal temperature increased 0.3 degrees C. alpha-MSH (100-400 micrograms) reduced the area under the fever curve an average of 50.0%, but had no effect on afebrile temperature. Molar equivalent amounts of the antipyretic drug acetaminophen had little effect on fever. These findings support the idea, based on research on rabbits, that alpha-MSH has a role in central modulation of fever.
Insights
Alpha-melanocyte-stimulating hormone (alpha-MSH) effectively reduced fever in squirrel monkeys, supporting its role in fever modulation. This study extends previous findings from rabbits to primates.
Area of Science:
- Neuroendocrinology
- Immunology
- Primate Physiology
Background:
- Alpha-melanocyte-stimulating hormone (alpha-MSH) has demonstrated antipyretic properties in rabbits.
- The efficacy of alpha-MSH in modulating fever in higher species, particularly primates, remains largely undetermined.
Purpose of the Study:
- To investigate the potential of alpha-MSH as an antipyretic agent in a primate model.
- To determine if alpha-MSH can reduce fever induced by bacterial endotoxins in squirrel monkeys.
Main Methods:
- Squirrel monkeys were utilized as a primate model due to their reliable fever response to bacterial endotoxins.
- Endotoxin was administered intravenously, and alpha-MSH was administered following a 0.3°C increase in rectal temperature.
- Dose-response relationships for endotoxin and alpha-MSH were established in pilot studies.
Main Results:
- Alpha-MSH administration (100-400 micrograms) significantly reduced the area under the fever curve by an average of 50.0%.
- Alpha-MSH did not affect normal body temperature in afebrile states.
- Molar equivalent doses of acetaminophen showed minimal effect on endotoxin-induced fever.
Conclusions:
- Alpha-MSH exhibits significant antipyretic effects in squirrel monkeys, supporting its role in fever regulation.
- These findings suggest that alpha-MSH may be a key central modulator of fever in primates, similar to its role in rabbits.
- Alpha-MSH's efficacy in primates warrants further investigation for potential therapeutic applications in fever management.