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Am J Physiol Regul Integr Comp Physiol 274: R783-R789, 1998;
0363-6119/98 $5.00
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Vol. 274, Issue 3, R783-R789, March 1998

Microinjection of a cyclooxygenase inhibitor into the anteroventral preoptic region attenuates LPS fever

Thomas E. Scammell, John D. Griffin, Joel K. Elmquist, and Clifford B. Saper

Department of Neurology and Program in Neuroscience, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115

Considerable evidence supports the role of prostaglandins in fever production, but the neuroanatomic sites of prostaglandin synthesis that produce fever remain unknown. With the use of a novel microinjection technique, we injected the cyclooxygenase inhibitor ketorolac into the preoptic area (POA) to determine which preoptic regions produce the prostaglandins required for fever. Initial experiments demonstrated that intravenous ketorolac blocked the fever normally produced by lipopolysaccharide (LPS) 5 µg/kg iv. Microinjection of ketorolac into the POA had no effect on body temperature, and injection of artificial cerebrospinal fluid into the POA did not alter LPS fever. Injection of ketorolac into the anteroventral POA markedly decreased the fever produced by LPS, compared with injections into more rostral, caudal, or dorsal locations. These observations indicate that prostaglandin synthesis in the anteroventral preoptic region is necessary for the production of fever.

antipyresis; prostaglandin endoperoxide synthase; prostaglandin E2; body temperature; thermoregulation; autonomic system; preoptic area; hypothalamus; lipopolysaccharide


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