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The interleukin‐1‐induced increase of substance P in sympathetic ganglia is not mediated by ciliary neurotrophic factor

Interleukin‐1 (IL‐1) induction of substance P (SP) in cultured sympathetic ganglia requires a soluble intermediate molecule that is present in IL‐1 conditioned medium (IL‐1CM). One of the required intermediates is leukemia inhibitory factor (LIF; Shadiack et al., J Neurosci 13:2601–2609, 1993). In the present study we have examined the possibility that ciliary neurotrophic factor (CNTF) is another intermediate involved in the IL‐1 induction of sympathetic SP. CNTF mimics the action of IL‐1CM by raising both SP and choline acetyltransferase activity‐‐‐actions that are blocked by a specific neutralizing antiserum for CNTF. However, IL‐1CM and CNTF differ in their response to depolarizing agents: while KCl (40 mM) blocks the action of IL‐1CM (and LIF), it enhances the action of CNTF. Furthermore, neither CNTF bioactivity nor CNTF protein is detected in IL‐1CM. Neutralizing antiserum to CNTF fails to block the action of either IL‐1 or IL‐1CM, suggesting that neither a soluble nor a membrane‐bound form of the molecule is active in direct response to IL‐1 action. While Northern blots confirm the presence of both CNTF and CNTF receptor mRNA in neonatal ganglia, neither culturing nor IL‐1 treatment alters these mRNA levels. These data taken together suggest that while CNTF is present and possibly active in sympathetic ganglia, it is not a mediator of the IL‐1 induction of SP. © 1994 Wiley‐Liss, Inc.