Central administration of alpha-MSH antiserum augments fever in the rabbit.

alpha-Melanocyte-stimulating hormone (alpha-MSH) has a marked antipyretic action when given centrally or peripherally, and the concentration of this peptide within the septal region of the brain increases during fever. To assess the significance of endogenous central alpha-MSH in fever, antiserum was given to rabbits via a cannula implanted in the third cerebral ventricle. Each day for 3 days, the animals received 50 microliters of normal rabbit serum (NRS) or an equal volume of antiserum raised against alpha-MSH. Interleukin 1 (IL 1) was then injected intravenously to determine the effect of central immunoneutralization of alpha-MSH on the febrile response. Immunoneutralization markedly prolonged fever. The average rise in temperature and the area under the fever curve after IL 1 injection were also significantly increased. Antiserum treatment did not alter normal body temperature, and NRS had no effect on IL 1-induced fever. These results indicate that endogenous central alpha-MSH contributes to physiological limitation of fever and that the role of this peptide in temperature regulation is relevant to the febrile state but not to normothermia.