Evidence against adenosine 3′,5′-monophosphate as a mediator of fever in the brain

The aim of this study was to test the hypothesis that increased concentrations of adenosine 3',5'-monophosphate (cyclic AMP) in the pyrogen-sensitive preoptic/anterior hypothalamic region (PO/AH) mediate fever. Micro-injection of N 6-2'- O-dibutyryl adenosine 3',5'-monophosphate (db cyclic AMP) into the preoptic/anterior hypothalamic region in rats produced a dose-dependent fall in body temperature which is inconsistent with the proposal that the nucleotide mediates fever. Hyperthermia was observed in some rats in response to large doses of db cyclic AMP, but this response was associated with convulsions. Endogenous concentrations of cyclic AMP in the preoptic/anterior hypothalamic region, as well as in the cerebral cortex, liver, spleen, thymus, white fat and plasma were unaffected by the febrile response to the subcutaneous injection of yeast in rats. A rise in levels of cyclic AMP was observed in the skeletal muscle of rats treated with yeast. The data presented do not indicate that cyclic AMP is involved in the neuronal events mediating fever in the rat.