Brain distribution of cytokine mRNA induced by systemic administration of interleukin-1beta or tumor necrosis factor alpha.

Brain cytokine mRNA levels are impacted by systemic cytokines. For example, systemic interleukin-1beta (IL1beta) increases brain IL1beta mRNA; subdiaphragmatic vagotomy blocks this effect. To localize which brain regions respond to intraperitoneal cytokines, we measured mRNA levels in selected brain regions for a variety of cytokines and growth factors, IL1beta, TNFalpha, interleukin-6 (IL-6), interleukin-10 (IL10), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). Relative to saline administration, IL1beta increased IL1beta, TNFalpha and IL6 mRNAs in the nucleus tractus solitarius (NTS), hypothalamus, hippocampus and somatosensory cortex (SSctx), but did not induce any changes in IL10. TNFalpha also increased TNFalpha and IL1beta mRNAs in the hypothalamus, hippocampus and SSctx. TNFalpha increased TNFalpha, IL1beta and IL10 mRNAs in the NTS, but did not induce any changes in IL-6 mRNA. In the amygdala, IL1beta enhanced IL6 mRNA and TNFalpha increased IL1beta mRNAs. In the insular cortex, IL1beta enhanced IL6 mRNA and TNFalpha increased IL1beta mRNA. TNFalpha administration increased NGF mRNA in the SSctx but decreased NGF and BDNF mRNA levels in the insular cortex. Both IL1beta and TNFalpha decreased BDNF mRNA in the amygdala. We also verified the IL1beta-induced increases in TNFalpha mRNA within the NTS using in situ hybridization. These results support the hypothesis that somnogenic doses of IL1beta and TNFalpha enhance their own mRNA levels as well as affect mRNA levels for other sleep-promoting substances.