Vagal CCK and 5-HT3 receptors are unlikely to mediate LPS or IL-1 beta-induced fever

Previous studies suggested that peripheral immune mediators may involve int ermediates acting on the vagus nerve, such as CCK or serotonin (5-HT). We h ave therefore investigated a possible role for vagal CCK-A and 5-HT3 recept ors in the febrile response after intraperitoneal human recombinant interle ukin-1 beta (IL-1 beta) or lipopolysaccharide (LPS). Unanesthetized, adult male rats instrumented with abdominal thermistors were given intraperitonea l CCK-8 sulfate (100 or 150 mg/kg) or 2-methyl-5-hydroxytryptamine maleate (4 mg/kg). In other experiments, rats were treated with either antagonists to the 5-HT3 receptor (ondansetron HCl; 100 mu g/kg) or the CCK-A receptor (L-364,718, 100 or 200 mu g/kg) in combination with LPS or IL-1 beta. CCK a dministration caused a short-lived hypothermia, but interference with the a ction of endogenous CCK at CCK-A receptors was without effect on IL-1 beta- or LPS-induced fever. Neither activation of 5-HT3 receptors nor blockade o f 5-HT3 receptors affected body temperature or LPS fever. Taken together, o ur data support the idea that vagal afferents responsive to pyrogenic cytok ines may be different from those responsive to CCK or 5-HT.