Effects of vagotomy on lipopolysaccharide-induced brain interleukin-1β protein in rats

The production of interleukin-1β (IL-1β) in brain is thought to be a critical step in the induction of central manifestations of the acute phase response, and the vagus nerve has been implicated in immune-to-brain communication. Thus, this study examined the effects of intraperitoneal (i.p.) injections of lipopolysaccharide (LPS) on brain IL-1β protein levels in control and subdiaphragmatically vagotomized rats. In the first experiment, vagotomized and sham-operated male Sprague–Dawley rats were injected i.p. with one of three doses (10, 50, 100 μg/kg) of LPS or vehicle (sterile, pyrogen-free saline) and sacrificed 2 h after the injection. In the second experiment, vagotomized and sham-operated rats were injected i.p. with 100 μg/kg LPS or vehicle and sacrificed 1 h after the injection. The i.p. injection of LPS dose-dependently increased IL-1β protein levels in the hypothalamus, hippocampus, dorsal vagal complex, cerebellum, posterior cortex, and pituitary 2 h after the injection. Brain and pituitary IL-1β levels were also significantly increased 1 h after the injection of 100 μg/kg LPS. There were no significant differences in brain IL-1β levels between sham-operated and vagotomized rats at either the 2 h or 1 h time points. The current data are consistent with previous studies showing increases in brain IL-1β after peripheral injections of LPS, and support the notion that brain IL-1β is a mediator in the illness-induction pathway. Furthermore, these data indicate that, at the doses and times tested, subdiaphragmatic vagal afferents are not crucial for LPS-induced brain IL-1β protein.