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The effect of alpha-MSH on fever caused by Staphylococcus aureus cell walls in rabbits
1Department of Physiology, University of the Witwatersrand Medical School, Parktown, South Africa.
Abstract:
The role of endogenous pyrogens induced by gram-positive bacterial pyrogens is not known. Intravenous alpha-MSH (2.5 micrograms) significantly reduced only the first phase of the biphasic thermal response to IV S. aureus cell walls (5 x 10(7)). Intracerebroventricular alpha-MSH (200 ng) had no effect on the fever response. The fall in serum iron concentration was significantly attenuated by the IV alpha-MSH but was not affected by the ICV alpha-MSH. Intravenous alpha-MSH had no effect on fever or the serum iron response caused by muramyl dipeptide (MDP). We conclude that the first phase of the thermal response to S. aureus cell walls is mediated by an endogenous pyrogen (EP) and the second phase of the response by a mechanism not involving EP, but possibly a muramyl peptide.
Insights
Alpha-melanocyte-stimulating hormone (alpha-MSH) given intravenously reduced the initial fever response to Staphylococcus aureus cell walls. This intravenous alpha-MSH also attenuated the drop in serum iron, suggesting a role for endogenous pyrogens in fever.
Area of Science:
- Immunology
- Neuroendocrinology
- Bacterial Pathogenesis
Background:
- Endogenous pyrogens (EPs) mediate fever responses to bacterial stimuli.
- The specific role of EPs in gram-positive bacterial pyrogen-induced fever is not fully understood.
- Alpha-melanocyte-stimulating hormone (alpha-MSH) is a key neuroendocrine mediator with anti-inflammatory properties.
Purpose of the Study:
- To investigate the role of endogenous pyrogens in the fever response to Staphylococcus aureus cell walls.
- To determine the effect of alpha-MSH on fever and associated physiological changes induced by bacterial components.
- To differentiate the mechanisms underlying biphasic fever responses.
Main Methods:
- Intravenous and intracerebroventricular administration of alpha-MSH in a rabbit model.
- Induction of fever using Staphylococcus aureus cell walls and muramyl dipeptide (MDP).
- Monitoring of body temperature and serum iron concentration.
Main Results:
- Intravenous alpha-MSH significantly reduced the first phase of fever induced by S. aureus cell walls.
- Intracerebroventricular alpha-MSH had no effect on the fever response.
- Intravenous alpha-MSH attenuated the decrease in serum iron, while intracerebroventricular administration did not.
- Alpha-MSH did not affect fever or serum iron response to muramyl dipeptide (MDP).
Conclusions:
- The first phase of S. aureus cell wall-induced fever is mediated by an endogenous pyrogen.
- The second phase of this fever response appears to involve a mechanism independent of EPs, potentially related to muramyl peptides.
- Intravenous alpha-MSH modulates fever and iron metabolism during gram-positive bacterial pyrogen challenge.