Protective effect of ciliary neurotrophic factor (CNTF) in a model of endotoxic shock: Action mechanisms and role of CNTF receptor α

M. T. Demitri, F. Benigni, C. Meazza, M. Zinetti, M. Fratelli, P. Villa, A. Acheson, N. Panayotatos, P. Ghezzi

Research output: Contribution to journalArticlepeer-review

Abstract

Ciliary neurotrophic factor (CNTF) inhibits the production of tumor necrosis factor (TNF) in lipopolysaccharide (LPS)-treated mice and protects against LPS lethality when coadministered with its soluble receptor (sCNTFRα). Both of these activities are abolished in adrenalectomized (ADX) mice. LPS-induced pulmonary polymorphonuclear neutrophil (PMN) infiltration and nitric oxide (NO) production were also inhibited by CNTF + sCNTFRα but not by CNTF alone. sCNTFRα did not alter the clearance or tissue distribution of CNTF. Furthermore, CNTF variants coadministered with sCNTFRα protected against LPS toxicity in a manner related to their affinity for the β components of CNTFR. Thus, inhibition of TNF production and protection against LPS lethality by CNTF/sCNTFRα require an intact hypothalamus- pituitary-adrenal axis (HPAA) and may be mediated by endogenous glucocorticoids. This protective effect is, at least in part, due to the inhibition of PMN infiltration and NO production, and appears to be mediated by cells displaying only β-receptor subtypes.

Original languageEnglish
Pages (from-to)47-55
Number of pages9
JournalJournal of Inflammation (United Kingdom)
Volume48
Issue number2
Publication statusPublished - 1998

Keywords

  • Ciliary neurotrophic factor
  • Hypothalamus-pituitary-adrenal axis
  • Neutrophil
  • Nitric oxide
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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