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Evidence for the involvement of adenosine 3',5'-cyclic monophosphate in fever genesis
Abstract:
In rabbit cerebrospinal fluid (CSF) during fever induced by endotoxins, myxoviruses, or endogenous pyrogen, concentrations of adenosine 3',5'-cyclic monophosphate (cyclic AMP) and prostaglandin E (PGE) are about 2-fold higher in comparison to normal values. In endotoxin treated animals paracetamol reduced the fever reaction and both PGE and cyclic AMP levels. Administration of theophyllin together with endotoxin enhanced the fever reaction and cyclic AMP levels in CSF, but had no influence on stimulation of PGE synthesis. Following injection of PGE2 into the lateral cerebral ventricles increased cyclic AMP concentrations were found in CSF. The results suggest, that the pyrogenic effect of PGE is mediated by stimulation of cerebral cyclic AMP synthesis.
Insights
Fever involves increased adenosine 3
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Fever involves complex physiological responses.
- Prostaglandin E (PGE) and cyclic adenosine monophosphate (cAMP) are implicated in fever regulation.
Purpose of the Study:
- To investigate the roles of PGE and cAMP in fever.
- To elucidate the mechanism of pyrogenic effects of PGE.
Main Methods:
- Inducing fever in rabbits using endotoxins, myxoviruses, or endogenous pyrogen.
- Measuring CSF concentrations of PGE and cAMP.
- Administering paracetamol and theophylline to endotoxin-treated rabbits.
- Injecting PGE2 into cerebral ventricles.
Main Results:
- Fever induced by various agents elevated CSF PGE and cAMP levels.
- Paracetamol reduced fever, PGE, and cAMP.
- Theophylline enhanced fever and cAMP but not PGE.
- PGE2 injection increased CSF cAMP.
Conclusions:
- PGE's pyrogenic effect is mediated by stimulating cerebral cAMP synthesis.
- This study clarifies the biochemical pathways involved in fever.