Dittrich F, Thoenen H, Sendtner M
Max-Planck-Institute for Psychiatry, Department of Neurochemistry, Planegg-Martinsried, Germany.
Ann Neurol. 1994 Feb;35(2):151-63. doi: 10.1002/ana.410350206.
Ciliary neurotrophic factor (CNTF) supports the survival of motoneurons in vitro and in vivo. Recombinant CNTF is an investigational drug for the treatment of amyotrophic lateral sclerosis. We determined the pharmacokinetics of radioiodinated CNTF after intravenous injection into rats. CNTF shows a biphasic clearance with an initial plasma half-life of 2.9 minutes and is removed from the circulation by the liver. No accumulation of radioactivity was detectable in nerve tissue or skeletal muscle after intravenous injection of 0.1 microgram and 0.5 microgram of CNTF. Radioactive degradation products accumulate in the skin. Liver cells express specific binding proteins for CNTF, and the incorporation and degradation of intravenously injected CNTF by the liver may occur after association of CNTF with the soluble CNTF receptor alpha in the circulation. Probably as a consequence of its binding to hepatocytes, CNTF induces acute-phase responses in liver. The short half-life and the inflammatory side effect may limit the clinical usefulness of systematically administered CNTF in the treatment of human motoneuron disorders.
睫状神经营养因子（CNTF）在体外和体内均能支持运动神经元的存活。重组CNTF是一种用于治疗肌萎缩侧索硬化症的研究性药物。我们测定了大鼠静脉注射放射性碘标记的CNTF后的药代动力学。CNTF表现出双相清除，初始血浆半衰期为2.9分钟，且通过肝脏从循环中清除。静脉注射0.1微克和0.5微克的CNTF后，在神经组织或骨骼肌中未检测到放射性积累。放射性降解产物在皮肤中积累。肝细胞表达CNTF的特异性结合蛋白，静脉注射的CNTF在循环中与可溶性CNTF受体α结合后，肝脏可能会对其进行摄取和降解。CNTF可能由于其与肝细胞的结合而在肝脏中诱导急性期反应。半衰期短和炎症副作用可能会限制系统性给药的CNTF在治疗人类运动神经元疾病中的临床应用。
