Plata-Salamán C R, Ilyin S E
Division of Molecular Biology, School of Life and Health Sciences, University of Delaware, Newark 19716-2590, USA.
J Neurosci Res. 1997 Sep 1;49(5):541-50. doi: 10.1002/(SICI)1097-4547(19970901)49:5<541::AID-JNR4>3.0.CO;2-B.
Interleukin-1beta (IL-1beta) induces anorexia, fever, sleep changes, and neuroendocrine alterations when administered into the brain. Here, we investigated the regulation of the IL-1beta system (ligand, receptors, receptor accessory protein, and receptor antagonist), tumor necrosis factor-alpoha (TNF-alpha), transforming growth factor (TGF)-beta1, and TGF-alpha mRNAs in the hypothalamus of obese (fa/fa) and lean (Fa/Fa) Zucker rats in response to the intracerebroventricular microinfusion of IL-1beta (8.0 ng/24 hr for 72 hr, a dose that yields estimated pathophysiological concentrations in the cerebrospinal fluid). IL-1beta increased IL-1beta, IL-1 receptor types I and II (IL-1RI and IL-1RII), IL-1 receptor accessory protein soluble form (IL-1R AcP II), IL-1 receptor antagonist (IL-1Ra), TNF-alpha, and TGF-beta1 mRNAs in the hypothalamus from obese and lean rats. IL-1beta-induced IL-1beta system and ligand (IL-1beta, TNF-alpha, and TGF-beta1) mRNA profiles were highly intercorrelated in the same samples. Levels of membrane-bound IL-1R AcP and TGF-alpha mRNAs did not change. Heat-inactivated IL-1beta had no effect. The data suggest 1) the operation of an IL-1beta feedback system (IL-1beta/IL-1RI/IL-1R Acp II/IL-1RII/IL-1Ra) and 2) potential cytokine-cytokine interactions with positive (IL-1beta <--> TNF-alpha) and negative (TGF-beta1 --> IL-1beta/TNF-alpha) feedback. Dysregulation of the IL-1beta feedback system and the TGF-beta1/IL-1beta-TNF-alpha balance may have implications for neurological disorders associated with high levels of IL-1beta in the brain.
白细胞介素-1β（IL-1β）注入脑内时会引发厌食、发热、睡眠改变以及神经内分泌改变。在此，我们研究了肥胖（fa/fa）和瘦（Fa/Fa） Zucker大鼠下丘脑内IL-1β系统（配体、受体、受体辅助蛋白和受体拮抗剂）、肿瘤坏死因子-α（TNF-α）、转化生长因子（TGF）-β1和TGF-α mRNA对脑室内微量注入IL-1β（8.0 ng/24小时，持续72小时，该剂量可在脑脊液中产生估计的病理生理浓度）的反应。IL-1β增加了肥胖和瘦大鼠下丘脑内的IL-1β、I型和II型IL-1受体（IL-1RI和IL-1RII）、IL-1受体辅助蛋白可溶性形式（IL-1R AcP II）、IL-1受体拮抗剂（IL-1Ra）、TNF-α和TGF-β1 mRNA。在相同样本中，IL-1β诱导的IL-1β系统和配体（IL-1β、TNF-α和TGF-β1）mRNA谱高度相关。膜结合型IL-1R AcP和TGF-α mRNA水平未发生变化。热灭活的IL-1β无作用。数据表明：1）存在一个IL-1β反馈系统（IL-1β/IL-1RI/IL-1R Acp II/IL-1RII/IL-1Ra）；2）潜在的细胞因子-细胞因子相互作用，包括正反馈（IL-1β <--> TNF-α）和负反馈（TGF-β1 --> IL-1β/TNF-α）。IL-1β反馈系统和TGF-β1/IL-1β-TNF-α平衡的失调可能与大脑中IL-1β水平升高相关的神经疾病有关。
