Cytokine mRNA induction by interleukin-1β or tumor necrosis factor α in vitro and in vivo

Hypothalamic and cortical mRNA levels for cytokines such as interleukin-1 beta (IL1 beta), tumor necrosis factor alpha (TNF alpha), nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) are impacted by systemic treatments of IL1 beta and TNF alpha. To investigate the time course of the effects of IL1 beta and TNF alpha on hypothalamic and cortical cytokine gene expression, we measured mRNA levels for TNFa, interleukin-6 (IL-6), interleukin-10 (IL-10), IL1 receptor 1, BDNF, NGF, and glutamate decarboxylase-67 in vitro using hypothalamic and cortical primary cultures. 11,11 and TNFa mRNA levels increased significantly in a dose-dependent fashion after exposure to either IL1 beta or TNF alpha. IL1 beta increased IL1 beta mRNA in both the hypothalamic and cortical cultures after 2-6 h while TNFa mRNA increased significantly within 30 min and continued to rise up to 2-6 h. Most of the other mRNAs showed significant changes independent of dose in vitro. In vivo, intracerebroventricular (icv) injection of IL1 beta or TNFa also significantly increased IL1 beta, TNF alpha and IL6 mRNA levels in the hypothalamus and cortex. IL1 beta icv, but not TNF alpha, increased NGF mRNA levels in both these areas. Results support the hypothesis that centrally active doses of IL1 beta and TNF alpha enhance their own mRNA levels as well as affect mRNA levels for other neuronal growth factors. (C) 2008 Elsevier B.V. All rights reserved.