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The mechanism of the pyrogenic effect of streptococcus cell wall mucopeptide
Abstract:
1. The intravenous injection into rabbits of 25-50 mug of a preparation of cell-wall mucopeptide (SM) from group A streptococcus produced a rise in rectal temperature and a fall in the number of circulating granulocytes in the blood.2. The pyrogenic response to SM is not dependent on the circulating granulocytes since it occurred also in rabbits made leucopenic by nitrogen mustard (HN 3).3. The pyrogenic response to SM was enhanced after an intravenous injection of 5-hydroxytryptophan (5-HTP).4. Pre-treatment with reserpine caused a much greater attenuation of the pyrogenic response to SM than pre-treatment with alpha-methyl-para-tyrosine (AMPT).5. As the reserpine reduced the 5-hydroxytryptamine (5-HT) and noradrenaline level in the hypothalamus, whereas the AMPT reduced only the noradrenaline level, it is concluded that 5-HT may be involved in the pyrogenic response and the way in which 5-HT may exert this function is discussed.
Insights
Group A streptococcus mucopeptide (SM) causes fever in rabbits, independent of granulocytes. This pyrogenic response is modulated by 5-hydroxytryptophan and involves serotonin.
Area of Science:
- Immunology
- Microbiology
- Neuroscience
Background:
- Group A Streptococcus cell-wall mucopeptide (SM) is a known pyrogen.
- The precise mechanisms underlying SM-induced fever and its interaction with immune cells are not fully understood.
Purpose of the Study:
- To investigate the role of circulating granulocytes in the pyrogenic response to SM.
- To explore the influence of neurotransmitters, specifically serotonin and noradrenaline, on SM-induced fever.
Main Methods:
- Intravenous administration of SM to rabbits.
- Induction of leucopenia using nitrogen mustard (HN3).
- Administration of 5-hydroxytryptophan (5-HTP), reserpine, and alpha-methyl-para-tyrosine (AMPT) to assess their effects on the pyrogenic response.
Main Results:
- SM induced fever and decreased circulating granulocytes in rabbits.
- The pyrogenic response persisted in leucopenic rabbits, indicating independence from granulocytes.
- 5-HTP enhanced the pyrogenic response to SM.
- Reserpine, which depletes hypothalamic serotonin and noradrenaline, significantly attenuated the SM-induced fever more than AMPT, which primarily reduces noradrenaline.
Conclusions:
- The pyrogenic response to streptococcal mucopeptide is not dependent on circulating granulocytes.
- Serotonin (5-HT) appears to play a significant role in mediating the pyrogenic effects of SM.
- These findings suggest a neuro-immune interaction in fever pathogenesis involving bacterial components and central neurotransmitter systems.