Vagal CCK and 5-HT3receptors are unlikely to mediate LPS or IL-1β-induced fever

Previous studies suggested that peripheral immune mediators may involve intermediates acting on the vagus nerve, such as CCK or serotonin (5-HT). We have therefore investigated a possible role for vagal CCK-A and 5-HT3receptors in the febrile response after intraperitoneal human recombinant interleukin-1β (IL-1β) or lipopolysaccharide (LPS). Unanesthetized, adult male rats instrumented with abdominal thermistors were given intraperitoneal CCK-8 sulfate (100 or 150 μg/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 μg/kg) or the CCK-A receptor (L-364,718, 100 or 200 μg/kg) in combination with LPS or IL-1β. CCK administration caused a short-lived hypothermia, but interference with the action of endogenous CCK at CCK-A receptors was without effect on IL-1β- or LPS-induced fever. Neither activation of 5-HT3 receptors nor blockade of 5-HT3 receptors affected body temperature or LPS fever. Taken together, our data support the idea that vagal afferents responsive to pyrogenic cytokines may be different from those responsive to CCK or 5-HT.