FORMATION OF INTERLEUKIN-6 IN THE BRAIN OF THE FEBRILE CAT - RELATIONSHIP TO INTERLEUKIN-1

Previous investigations have shown that interleukin-6 (IL-6), unlike o ther cytokines, is produced in larger amounts in the brain of the febr ile animal regardless of the route, peripheral vs. central, of pyrogen administration. In addition, depending on the experimental condition IL-6 production may or may not require the prior induction of interleu kin-1 (IL-1). The present study was carried out in the conscious cat t o assess the importance of brain-derived IL-6 in the pathogenesis of f ever and the interaction at that site between this cytokine and IL-1. IL-6 was detected in cerebrospinal fluid (CSF) collected at rest and i ts levels increased during the fever to intravenous (i.v.) endotoxin. The IL-6 elevation, but not the fever, was reversed by pretreatment wi th intracerebroventricular (i.c.v.) IL-1 receptor antagonist (hIL-1ra) . Conversely, when pyrogens (endotoxin, IL-1) were given i.c.v., i.c.v . hIL-1ra reduced the fever without altering significantly the associa ted rise in CSF IL-6. We conclude that IL-6 is formed in brain in resp onse to both i.v. and i.c.v. pyrogens; however, its formation, whether requiring the prior induction of IL-1 or not, does not appear to be c ritical for the development of the fever. Blood-borne IL-6, unlike bra in-derived IL-6, may still play a role in fever as a trigger of signal -transducing mechanisms operating across the blood-brain barrier. (C) 1998 Elsevier Science B.V. All rights reserved.