Evidence supporting a role for endogenous vasopressin in fever suppression in the rat.

1. Infusion of human purified interleukin‐1 into a lateral cerebral ventricle of the rat evoked a rise in core temperature which was abolished by heating the interleukin‐1. 2. When the intracerebroventricular infusion of interleukin‐1 was preceded by a bilateral injection of saline into the ventral septal area, the resulting febrile response was not different from that induced by interleukin‐1 alone. However, when the vasopressin V1 antagonist, d(CH2)5Tyr(Me)AVP, was injected into the ventral septal area prior to interleukin‐1, a fever was evoked which was significantly greater in magnitude and duration. This enhancement of fever by the V1 antagonist was dose related. 3. Injection of either saline or the V1 antagonist into the ventral septal area, in the absence of interleukin‐1, did not evoke any consistent alteration in the core temperature of the rats. 4. The vasopressin V2 antagonist, d(CH2)5‐D‐ValVAVP, was injected into the ventral septal area to determine the effect of another vasopressin analogue on the fever evoked by interleukin‐1. The V2 antagonist did not alter the time course of interleukin‐1‐induced fever or alter core temperature in the afebrile rat. 5. These data are consistent with the hypothesis that endogenous vasopressin, released in the ventral septal area, may be involved in limiting fever. In addition, these results indicate that the central receptor mediating the antipyretic action of vasopressin may resemble the V1 subtype of peripheral vasopressin receptor.