Persistence of febrile response to pyrogens after PO/AH lesions in squirrel monkeys.

Observation of a patient who developed fever in spite of severe CNS sarcoidosis led us to test the idea that febrile responses require mediation by neurons in the preoptic/anterior hypothalamic (PO/AH) region. Changes in rectal and skin temperatures and oxygen consumption were recorded after intravenous and intracerebroventricular injections of endotoxin, after intracerebroventricular prostaglandin E1 (PGE1), and after intravenous injections of leukocyte pyrogens in animals in which the PO/AH region had been destroyed. The capacity to develop fever persisted after PO/AH destruction, and the patterns of heat production and heat loss were unchanged. Pyrogens were still effective after intracerebroventricular 6-hydroxydopamine and intraperitoneal reserpine given to reduce brain amines in monkeys with PO/AH lesions. It is unlikely that a secondary control in the medulla oblongata is responsible for the persisting sensitivity to pyrogens, since multiple injections of endotoxin into this region did not cause fever either before or after the PO/AH region was destroyed. The results do not support the idea that control of fever is localized in the PO/AH region alone. Rather, it appears that in the brains of primates there is either multiple central representation of fever control or an inherent capacity to develop sensitivity to pyrogens and to produce coordinated febrile responses.