Nitric oxide regulates body temperature, neuronal activation and interleukin-1 beta gene expression in the...

An immune challenge initiates a complex cascade of events in the body including important responses from the central nervous system. As nitric oxide (NO) has been implicated in the central regulation of neuroendocrine and autonomic responses, this study was performed to determine if NO regulates physiological responses, neuronal activation, and/or interleukin-1 beta (IL-1 beta) gene expression in the paraventricular nucleus of the rat hypothalamus (PVN) in response to intravenous endotoxin, lipopolysaccharide (LPS, 100 microg/kg). Intracerebroventricular injections of NO synthase (NOS) inhibitors (7-nitroindazole sodium salt for neuronal NOS, N(G)-nitro-L-arginine for neuronal NOS and endothelial NOS, and aminoguanidine for inducible NOS) in LPS-treated rats showed that inhibition of NOS eliminated the drop in body temperature and led to increased neuronal activation in the PVN as assessed by immunohistochemistry for Fos-like immunoreactivity. Activation of NO-producing PVN neurons was also increased in these rats suggesting that NO influences neuronal NOS activity in PVN neurons. Finally, increased IL-1 beta gene expression in the PVN of LPS-treated rats receiving N(G)-nitro-L-arginine showed that NO regulates brain IL-1 beta gene expression. The results obtained with the NOS inhibitors support the hypothesis that NO produced from eNOS in the brain participates in temperature regulation, and inhibits PVN neuronal activity and IL-1 beta gene expression during immune stress.