A hypothalamic region responsive to localized injection of pyrogens.

Abstract

Colonic temperatures were recorded following microinjection of leukocytic pyrogen at 61 intracerebral loci, and of pyrogen free saline (0.9%) and typhoid vaccine at many of these loci. With adequate procedural safeguards, more than 90% of the saline injections evoked no febrile response. Injection of 2-5 ul. of leukocytic pyrogen into the dorsal portion of the anterior hypothalamus, behind and below the anterior commisure, elicited fevers which had latencies of 5 minutes or less, peaked within 60 minutes, and subsided promptly. No fevers followed similar injections into the posterior hypothalamus, the thalamus, or the pre-optic area. The fever area thus delimited was a block of tissue less than 4.5 mm3 in volume on each side of the midline. Typhoid vaccine similarly injected into relatively large portions of the middle and anterior hypothalamus evoked febrile responses which had latencies of 30-60 minutes and persisted for over 700 minutes. These responses were similar in time course to the occasional (less than 10%) febrile responses recorded following control microinjections of saline. Intrahypothalamic injection of pyrogens constitutes a bioasay system which is so sensitive that it can clearly distinguish between the temperature responses evoked by very small quantities of leukocytic pyrogen and of endotoxin.