FEVER SUPPRESSION BY SUBDIAPHRAGMATIC VAGOTOMY IN GUINEA-PIGS DEPENDSON THE ROUTE OF PYROGEN ADMINISTRATION

It has recently been shown that subdiaphragmatic vagotomy blocks some of the effects of inflammatory stimuli on brain-controlled functions. Therefore, vagal afferent fibers have been proposed to play a prominen t role in the communication pathways between the immune system and the brain. In the present study, we investigated the effect of subdiaphra gmatic vagotomy on fever induced by intraperitoneal or intramuscular i njection of lipopolysaccharide (LPS) or muramyl dipeptide (MDP), which are both cytokine-inducing agents in guinea pigs. Intraperitoneal and intramuscular injections of LPS or MDP were tested in the same animal with an interval of 1 wk. In one experiment, intraperitoneal injectio ns of LPS or MDP were performed at the beginning, followed by intramus cular injections 1 wk later. In another experiment, intramuscular inje ctions of LPS or MDP were performed at the beginning, followed by intr aperitoneal injections 1 wk later. The febrile response to intraperito neal injection of LPS was almost completely abrogated in vagotomized a nimals compared with sham-operated controls (from 30-330 min after int raperitoneal injection of LPS). The suppression of LPS fever was quant itatively the same in both experiments. In contrast, the response to i ntramuscular injection of LPS was the same in vagotomized and sham-ope rated guinea pigs in each of the experiments. Fever induced by intrape ritoneal injection of MDP was partly attenuated by subdiaphragmatic va gotomy (between 150 and 300 min after intraperitoneal injection of MDP ) in both experiments. Again, the febrile response to intramuscular in jections of MDP was not significantly altered by subdiaphragmatic vago tomy. In conclusion, the suppressive effect of subdiaphragmatic vagoto my on fever induced by peripheral immune stimuli depends on the route of pyrogen administration. Because the febrile response to intraperito neal injection of bacterial pyrogens is strongly diminished in vagotom ized guinea pigs, it is suggested that vagal afferent fibers play a cr ucial role in the transduction of immune signals from the abdominal ca vity to the brain.