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 t o the group of cytokines causing fever in response to infectious and i nflammatory noxae. The present investigation was undertaken in the con scious cat to verify whether CNTF (human type, hCNTF) is pyrogenic whe n given either intravenously (IV) or intracerebroventricularly (ICV) a nd correlate at the same time body temperature with cerebrospinal flui d (CSF) levels of prostaglandin (PG) E-2 (i.e., the putative fever med iator 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) c aused fever by both routes and the increase in body temperature was as sociated with an upward change in CSF PGE,. Conversely, CSF TXB2 showe d 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)-pro moting actions sharing the signal-transducing mechanism with hCNTF. We conclude that CNTF lends itself to a role in the pathogenesis of feve r. The modest PGE(2) elevation relatively to other cytokines, specific ally hIL-1, is ascribed to the fact that CNTF activates the inducible isoform of arachidonate cyclooxygenase, which is constitutively expres sed in brain, without concomitantly promoting the formation of new enz yme. (C) 1998 Elsevier Science Inc.