Brain distribution of cytokine mRNA induced by systemic administration of interleukin-1β or tumor necrosis factor α

Brain cytokine mRNA levels are impacted by systemic cytokines. For example, systemic interleukin-1 beta (IL1 beta) increases brain IL1 beta 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, IL1 beta TNF alpha, interleukin-6 (IL-6), interleukin-10 (IL10), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). Relative to saline administration, IL1 beta increased IL1 beta, TNFa and IL6 mRNAs in the nucleus tractus solitarius (NTS), hypothalamus, hippocampus and somatosensory cortex (SSctx), but did not induce any changes in IL10. TNF alpha also increased TNFa and IL1 beta mRNAs in the hypothalamus, hippocampus and SSctx. TNF alpha increased TNF alpha, IL1 beta and IL10 mRNAs in the NTS, but did not induce any changes in IL-6 mRNA. In the amygdala, IL1 beta enhanced IL6 mRNA and TNF alpha increased IL10 mRNAs. In the insular cortex, IL1 beta enhanced IL6 mRNA and TNFa increased IL1 beta mRNA. TNF(x administration increased NGF mRNA in the SSctx but decreased NGF and BDNF mRNA levels in the insular cortex. Both IL10 and TNFa decreased BDNF mRNA in the amygdala. We also verified the ILI induced increases in TNFa mRNA within the NTS using in situ hybridization. These results support the hypothesis that somnogenic doses of IL1 beta and TNF alpha enhance their own mRNA levels as well as affect mRNA levels for other sleep-promoting substances. (c) 2006 Elsevier B.V. All rights reserved.