Vagotomy blocks the induction of interleukin-1β (IL-1β) mRNA in the brain of rats in response to systemic IL-1β

Abstract

There is considerable interest in the mechanisms by which systemic cytokines signal the CNS to elicit centrally controlled biological actions. This study determined the effects of intraperitoneal injections of interleukin-1β (IL-1β) on IL-1β mRNA and IL-1 receptor accessory protein (IL-1RAP) mRNA production in rat liver and brain using the reverse transcription-PCR. Saline or IL-1β (0.5 μg/kg) was injected intraperitoneally in subdiaphragmatically vagotomized and sham-operated (SHAM) rats. All injections were performed at dark onset, and rats were killed 2 hr after the injection. In SHAM rats, IL-lβ increased IL-1β mRNA levels in the liver, hypothalamus, hippocampus, and brainstem. Subdiaphragmatic vagotomy blocked the IL-1β-induced increase in IL-1β mRNA in the brainstem and hippocampus and significantly attenuated the in- crease in the hypothalamus. Vagotomy did not affect IL-1β induced IL-1β mRNA production in the liver. IL-1RAP mRNA was highly expressed in each region examined; however, no significant differences in IL-1 RAP mRNA production were found in any region after IL-1β injection. The current results indicate that the vagus nerve is involved in transmitting cytokine signals to the brain and suggest that the induction of brain cytokines is a critical step in the pathway by which vagal-mediated signals result in centrally controlled symptoms of the acute phase response.