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

Abstract

Brain cytokine mRNA levels are impacted by systemic cytokines. For example, systemic interleukin-1β (IL1β) increases brain IL1β 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, IL1β, TNFα, interleukin-6 (IL-6), interleukin-10 (IL10), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). Relative to saline administration, IL1β increased IL1β, TNFα and IL6 mRNAs in the nucleus tractus solitarius (NTS), hypothalamus, hippocampus and somatosensory cortex (SSctx), but did not induce any changes in IL10. TNFα also increased TNFα and IL1β mRNAs in the hypothalamus, hippocampus and SSctx. TNFα increased TNFα, IL1β and IL10 mRNAs in the NTS, but did not induce any changes in IL-6 mRNA. In the amygdala, IL1β enhanced IL6 mRNA and TNFα increased IL1β mRNAs. In the insular cortex, IL1β enhanced IL6 mRNA and TNFα increased IL1β mRNA. TNFα administration increased NGF mRNA in the SSctx but decreased NGF and BDNF mRNA levels in the insular cortex. Both IL1β and TNFα decreased BDNF mRNA in the amygdala. We also verified the IL1β-induced increases in TNFα mRNA within the NTS using in situ hybridization. These results support the hypothesis that somnogenic doses of IL1β and TNFα enhance their own mRNA levels as well as affect mRNA levels for other sleep-promoting substances.