Ciliary neurotrophic factor is an endogenous pyrogen.
Fever is initiated by the action of polypeptide cytokines called endogenous pyrogens, which are produced by the host during inflammation, trauma, or infection and which elevate the thermoregulatory set point in the hypothalamus. Ciliary neurotrophic factor (CNTF) supports the differentiation and survival of central and peripheral neurons. We describe the activity of CNTF as intrinsically pyrogenic in the rabbit. CNTF induced a monophasic fever which rose rapidly (within the first 12 min) following intravenous injection; CNTF fever was blocked by pretreatment with indomethacin. The fever induced by CNTF was not due to contaminating endotoxins. Increasing doses of CNTF resulted in prolongation of the fever, suggesting the subsequent induction of additional endogenous pyrogenic activity. After passive transfer of plasma obtained during CNTF-induced fever, endogenous pyrogen activity was not present in the circulation; CNTF also did not induce the endogenous pyrogens interleukin 1, tumor necrosis factor, or interleukin 6 in vitro. Nevertheless, a second endogenous pyrogen may originate within the central nervous system following the systemic injection of CNTF. Of the four endogenous pyrogens described to date (interleukin 1, tumor necrosis factor, interferon, and interleukin 6), CNTF, like interleukin 6, utilizes the cell-surface gp 130 signal-transduction apparatus.
Department of Medicine, Tuffs University School of Medicine, Boston, MA.
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Shapiro
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Zhang
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Rupp
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Wolff
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Dinarello
D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D020934:Ciliary Neurotrophic Factor; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000633:toxicity; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000502:physiology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D009414:Nerve Growth Factors / Q000633:toxicity; D009419:Nerve Tissue Proteins / Q000633:toxicity*; D011749:Pyrogens / Q000633:toxicity*; D011817:Rabbits; D011994:Recombinant Proteins / Q000633:toxicity*
D020934:Ciliary Neurotrophic Factor; D007375:Interleukin-1; D008070:Lipopolysaccharides; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011749:Pyrogens; D011994:Recombinant Proteins