Vasopressin and fever: evidence supporting the existence of an endogenous antipyretic system in the brain

Abstract

Vasopressin administered into the ventral septum exerts a dose-related antipyresis. This site of action is similar in a number of species. The fever-reducing properties of vasopressin are both site and neuropeptide specific. Evidence supporting a role for endogenous vasopressin in fever suppression is the demonstration that the release of the peptide from the ventral septal area is altered during fever: the amount released correlates negatively with febrile changes in body temperature. In addition, changes in the concentration of vasopressin in the septum and amygdala have been demonstrated immunocytochemically during fever: an activation of vasopressinergic neurons occurs which is similar to that observed in pregnant animals at term when fever is absent. Specific antibodies directed against vasopressin or specific vasopressin antagonist analogues (e.g., d(CH₂)₅Tyr(Me)AVP) enhanced the febrile response to a pyrogen challenge when injected into the ventral septum. The same antagonist also can antagonize the antipyretic effect of exogenously administered vasopressin. The use of relatively specific antagonists and agonists of vasopressin, directed against the V₁ and V₂ subtypes of the peripheral vasopressin receptor, suggests that the central receptor responsible for the antipyretic effect of vasopressin may resemble the V₁ subtype. Recent experiments using electrophysiological techniques have demonstrated the existence of thermoresponsive units in the ventral septal area whose activity may be altered by vasopressin which is possibly derived from the paraventricular nucleus and bed nucleus of the stria terminalis. Electrical stimulation of one of these cell groups in the paraventricular nucleus can reduce the fever evoked by systemic administration of bacterial pyrogen in the rabbit. Collectively, these data strongly support the hypothesis that a system of endogenous antipyresis involving vasopressin exists in the brain. There also may exist another antipyretic system in the brain involving α-melanotropin. This peptide is antipyretic when injected into the dorsal septum and concentrations of α-melanotropin are altered in this area of the brain during fever. Further, passive immunoneutralization using antiserum specific to α-melanotropin results in prolonged fever. A possible connection between the two systems has not yet been investigated. However, in future studies the mechanisms and significance of such a system will be investigated further.