Effect of ciliary neurotrophic factor on body temperature and cerebrospinal fluid prostanoids in the cat

It has been proposed that ciliary neurotrophic factor (CNTF) belongs to the group of cytokines causing fever in response to infectious and inflammatory noxae. The present investigation was undertaken in the conscious cat to verify whether CNTF (human type, hCNTF) is pyrogenic when given either intravenously (IV) or intracerebroventricularly (ICV) and correlate at the same time body temperature with cerebrospinal fluid (CSF) levels of prostaglandin (PG) E-2 (i.e., the putative fever mediator in brain) and thromboxane (TX) B-2 (the stable TXA(2) byproduct) in untreated vs, treated animals. hCNTF (10 mu g/kg IV; 1 mu g ICV) caused fever by both routes and the increase in body temperature was associated with an upward change in CSF PGE,. Conversely, CSF TXB2 showed no elevation. Similarly unaffected was CSF TXB2 by human interleukin 6 (hIL-6, 1 mu g ICV), a cytokine with known pyrogenic and PGE(2)-promoting actions sharing the signal-transducing mechanism with hCNTF. We conclude that CNTF lends itself to a role in the pathogenesis of fever. The modest PGE(2) elevation relatively to other cytokines, specifically hIL-1, is ascribed to the fact that CNTF activates the inducible isoform of arachidonate cyclooxygenase, which is constitutively expressed in brain, without concomitantly promoting the formation of new enzyme. (C) 1998 Elsevier Science Inc.