CILIARY NEUROTROPHIC FACTOR - PHARMACOKINETICS AND ACUTE-PHASE RESPONSE IN RAT

Ciliary neurotrophic factor (CNTF) supports the survival of motoneuron s in vitro and in vivo. Recombinant CNTF is an investigational drug fo r the treatment of amyotrophic lateral sclerosis. We determined the ph armacokinetics of radioiodinated CNTF after intravenous injection into rats. CNTF shows a biphasic clearance with an initial plasma half-lif e of 2.3 minutes and is removed from the circulation by the liver. No accumulation of radioactivity was detectable in nerve tissue or skelet al muscle after intravenous injection of 0.1 mu g and 0.5 mu g 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 aft er association of CNTF with the soluble CNTF receptor cr in the circul ation. Probably as a consequence of its binding to hepatocytes, CNTF i nduces acute-phase responses in liver. The short half-life and the inf lammatory side effect may limit the clinical usefulness of systematica lly administered CNTF in the treatment of human motoneuron disorders.