Since ciliary neurotrophic factor (CNTF) inhibits the production of TNF and activates the hypothalamus-pituitary-adrenal axis (HPAA), we investigated whether CNTF can produce antiinflammatory actions and whether it may act through a central mechanism, using the murine air pouch model of inflammation. In this model, inflammation is evaluated by measuring the induction of TNF and IL-6 as well as cell recruitment in the pouch fluid 24 h after carra-geenan. Intracerebroventricular injection, but not intravenous or local injection of CNTF markedly inhibited inflammation. This was associated with high serum corticosterone levels, and antiinflammatory action was not observed in adrenalectomized mice, indicating that an intact HPAA is required. A CNTF receptor antagonist increased carrageenan inflammation, suggesting that endogenous CNTF might have a centrally mediated antiinflammatory role.