Vagal CCK and 5-HT(3) receptors are unlikely to mediate LPS or IL-1beta-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-HT(3) receptors in the febrile response after intraperitoneal human recombinant interleukin-1beta (IL-1beta) or lipopolysaccharide (LPS). Unanesthetized, adult male rats instrumented with abdominal thermistors were given intraperitoneal CCK-8 sulfate (100 or 150 microgram/kg) or 2-methyl-5-hydroxytryptamine maleate (4 mg/kg). In other experiments, rats were treated with either antagonists to the 5-HT(3) receptor (ondansetron HCl; 100 microgram/kg) or the CCK-A receptor (L-364,718, 100 or 200 microgram/kg) in combination with LPS or IL-1beta. CCK administration caused a short-lived hypothermia, but interference with the action of endogenous CCK at CCK-A receptors was without effect on IL-1beta- or LPS-induced fever. Neither activation of 5-HT(3) receptors nor blockade of 5-HT(3) 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.