Abstract
Intracerebroventricular (i.c.v.) injection of arachidonic acid (AA) evokes fever. This response has been thought to occur simply because AA is converted to prostaglandin E2 (PGE2), the final mediator of fever, by constitutively expressed enzymes of the AA cascade. However, our recent study suggested that AA might not only be the precursor of PGE2 but also induce an enzyme cyclooxygenase-2 (COX-2) that catalyses AA to form prostaglandins. We here examined in rats whether AA-induced fever is dependent on COX-2, and, if so, where COX-2 is induced by AA. I.c.v. injection of AA evoked biphasic fever. The first phase started within 15 min of injection and peaked at 30 min. The second phase started at 60 min and peaked at 2 h after AA injection. COX-2 specific inhibitor completely suppressed the second phase of fever while COX-1 specific inhibitor suppressed the first phase. Two hours after AA injection, PGE2 level in the cerebrospinal fluid was elevated. This elevation was also suppressed by the COX-2 inhibitor. Immunohistochemistry and immunoblotting revealed enhanced COX-2 expression in subarachnoidal tissues. Double immunohistochemistry revealed that the major cell type that expressed COX-2 was endothelial cell. These results indicate that AA itself or its metabolite induces COX-2 expression that accelerates the formation of PGE2 from AA, and, hence, develops the second phase of fever. [J Physiol Sci. 2007;57 Suppl:S49]
