The contribution of the vagus nerve in interleukin-1 beta-induced fever isdependent on dose

It has been suggested that proinflammatory cytokines communicate to the bra in via a neural pathway involving activation of vagal afferents by interleu kin-1 beta (IL-1 beta), in addition to bloodborne routes. In support, subdi aphragmatic vagotomy blocks IL-1 beta -induced, brain-mediated responses su ch as fever. However, vagotomy has also been reported to be ineffective. Ne ural signaling would be expected to be especially important at low doses of cytokine, when local actions could occur, but only very small quantities o f cytokine would become systemic. Here, we examined core body temperature a fter intraperitoneal injections of three doses of recombinat human IL-1 bet a (rh-IL-1 beta). Subdiaphragmatic vagotomy completely blocked the fever pr oduced by 0.1 mug/kg, only partially blocked the fever produced by 0.5 mug/ kg, and had no effect at all on the fever that followed 1.0 mug/kg rh-IL-1 beta. Blood levels of rh-IL-1 beta did not become greater than normal basal levels of endogenous rat IL-beta until the 0.5-mug/kg dose nor was IL-1 be ta induced in the pituitary until this dose. These results suggest that low doses of intraperitoneal IL-1 beta induce fever via a vagal route and that dose may account for some of the discrepancies in the literature.