Diazepam inhibits stimulating effect of cooling preoptic area on antibody production

To clarify the mechanism of the stimulating effect of fever on the primary antibody response, rats were immunized with sheep erythrocytes, and a fever-like response was induced by cooling the preoptic area for five days. Diazepam, 0.5 mg/kg, given daily during the cooling time, did not affect the normal antibody response of the control animals nor did it prevent the rise in body temperature elicited by cooling the preoptic area but it did, nevertheless, strongly reduce the stimulating effect of this procedure on antibody production. A smaller reduction of this effect was also seen in adrenalectomized rats in which a physiological and stable plasma level of corticosterone was maintained. Because diazepam suppresses some sympathetic and endocrine responses to stress, these data suggest that the effect of cooling the preoptic area on the primary antibody response, and, by inference, that of fever, is to a large extent mediated by the adrenal and other stress response or responses to the cold stimulus. The results do not, however, exclude the possibility of an additional, direct effect of the elevated body temperature on immunocompetent cells.