INTERRELATED ADRENOCORTICAL AND NEUROHYPOPHYSEAL RESPONSES ASSOCIATEDWITH FEVER IN ENDOTOXIN-TREATED PIGS

Low intravenous doses of endotoxin [lipopolysaccharide (LPS), 0.7 mu g /kg] induce monophasic fever, increase anterior and posterior pituitar y hormone release, and enhance hypothalamic c-Fos expression in pigs, all of which can be prevented by indomethacin (Ind). The present study shows that the synthetic corticosteroid dexamethasone (Dex, 5 mg/kg) has a similar action to Ind and, when given alone, lowers core tempera ture. In addition, the corticosteroid synthesis inhibitor metyrapone ( Met, 3.3 mg/kg, every one-half hour) reduces LPS fever and amplifies t he effect of LPS on vasopressin, but not on oxytocin, release. The sim ilar actions of Dex and Ind suggest that phospholipase A(2) pathways c ontrolling prostaglandin synthesis mediate the responses of prepuberta l pigs to immunological challenge with LPS. The increased vasopressin release induced when animals receiving Met are also given LPS supports findings in other nonrodent species indicating an inverse relationshi p between cortisol and vasopressin. The attenuation of LPS fever by Me t is suggestive of an endogenous antipyretic mechanism associated with enhanced neurohypophysial vasopressin secretion.