Observations on the site & mode of action of pyrogens in the rabbit brain.

1. Leucocyte pyrogen has been injected bilaterally into various parts of the rabbit brain. It caused fever when injected into the pre-optic area and the anterior hypothalamus, but not when injected into the posterior hypothalamus, the mid-brain, the pons, the cerebellum or the cerebral cortex.2. The mean time which elapsed between a leucocyte pyrogen injection into the anterior hypothalamus and the onset of fever was 7.8 min. For similar injections of bacterial pyrogen the time lag was 24.8 min. The mean time lag between bilateral injections of noradrenaline into the anterior hypothalamus and the onset of fever was 7.4 min.3. The amount of leucocyte pyrogen required to cause fever when injected into the anterior hypothalamus was less than 1/100 of that required to cause a similar fever on intravenous injection. The quantity of bacterial pyrogen injected into the hypothalamus was of the same order as that which would cause a similar fever on intravenous injection.4. Control injections of saline, plasma, cerebrospinal fluid, heated leucocyte pyrogen and red cells into the anterior hypothalamus did not cause fever.5. After attempts to deplete the hypothalamus of its monoamine stores by intraventricular injections of reserpine, the rabbit had fever as a result of an intravenous injection of bacterial pyrogen.6. We conclude that the anterior hypothalamus and the pre-optic area are sites at which leucocyte pyrogen acts to cause fever in the rabbit. The mechanism of this febrile response is not clear, but it appears that part, at least, of the response could be mediated by a mechanism other than release of noradrenaline or failure to release 5-HT.