Partial elimination of vagal sensory afferents by subdiaphragmatic vagal section has variously been reported to eliminate, to reduce, or to have no effect on
fever produced by peripheral
lipopolysaccharide and
interleukin-1beta (IL-1beta). However, to adequately test the idea that vagal afferents convey immune information to the brain, all vagal input to the central nervous system must be eliminated. This was accomplished by bilateral electrolytic lesions of the nucleus tractus solitarius (NTS). Reflex
bradycardia evoked by intravenous
phenylbiguanide was eliminated in NTS-lesioned rats, verifying the lesion's effectiveness. IL-1beta (2 microg/kg) was given to conscious, unrestrained rats via an indwelling intraperitoneal
catheter and produced rapid
fever (approximately 1 degree C) with an onset latency of 15 min and peak response at 30 min, with a second, smaller peak
at 130 min. NTS lesions attenuated the first
fever peak, with a lesser, non-significant effect on the second peak. The thermogenic capacity of NTS-lesioned rats was evaluated using 3 different strategies: (1) thermogenesis evoked by CNS
injections of
prostaglandin E2, (2) 3 h exposure to a 4 degrees C environment, and (3) heat production of intrascapular brown fat produced by
intravenous infusion of the beta3-adrenergic agonist
BRL 37344. NTS-lesioned rats were equivalent, or even superior to control animals in their thermogenic response to these non-immune-related stimuli. Therefore, the impaired febrile response of NTS-lesioned rats to IL-1beta cannot be attributed to reduced thermogenic capacity. Finally, these results suggest that
fever elicited by intraperitoneal IL-1beta is, at least in part, dependent on the integrity of NTS neurons, but also that mechanisms independent of vagal afferent projections to the NTS must also play a role in immune-to-brain signaling.