TNF-alpha-induced corticosterone elevation but not serum protein or corticosteroid binding globulin reduction is vagally mediated.

Immune activation leads to production of mediators such as cytokines, which act to induce both brain-mediated and peripheral defense processes. We used intraperitoneal administration of the cytokine tumor necrosis factor-alpha (TNF-alpha) to investigate whether defense processes induced by this cytokine are mediated by vagal afferents and/or interleukin-1 (IL-1) receptors. Because some effects of TNF-alpha are mediated, at least in part, by the brain [plasma corticosterone (CORT) elevation] and some are mediated by peripheral organs [reduction of serum protein and corticosteroid binding globulin (CBG)], we also investigated whether the effects of vagotomy are specific to those defense processes mediated by the brain. Both vagotomy and IL-1 receptor antagonist attenuated serum CORT elevation, but had no effects on serum protein or CBG reduction. These results support the idea that vagal afferents provide a true immune-to-brain pathway that may include IL-1 receptors.