Continued administration of ciliary neurotrophic factor protects mice from inflammatory pathology in experimental autoimmune encephalomyelitis.

Abstract

Multiple sclerosis is an inflammatory disease of the central nervous system that leads to loss of myelin and oligodendrocytes and damage to axons. We show that daily administration (days 8 to 24) of murine ciliary neurotrophic factor (CNTF), a neurotrophic factor that has been described as a survival and differentiation factor for neurons and oligodendrocytes, significantly ameliorates the clinical course of a mouse model of multiple sclerosis. In the acute phase of experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte glycoprotein peptide 35-55, treatment with CNTF did not change the peripheral immune response but did reduce the number of perivascular infiltrates and T cells and the level of diffuse microglial activation in spinal cord. Blood brain barrier permeability was significantly reduced in CNTF-treated animals. Beneficial effects of CNTF did not persist after it was withdrawn. After cessation of CNTF treatment, inflammation and symptoms returned to control levels. However, slight but significantly higher numbers of oligodendrocytes, NG2-positive cells, axons, and neurons were observed in mice that had been treated with high concentrations of CNTF. Our results show that CNTF inhibits inflammation in the spinal cord, resulting in amelioration of the clinical course of experimental autoimmune encephalomyelitis during time of treatment.

• Authors: Tanja Kuhlmann, Leah Remington, Isabelle Cognet, Lyne Bourbonniere, Simone Zehntner, Florence Guilhot, Alexandra Herman, Angélique Guay-Giroux, Jack P Antel, Trevor Owens, Jean-François Gauchat
• Journal: The American journal of pathology (Am J Pathol) Vol. 169 Issue 2 Pg. 584-98 (Aug 2006) ISSN: 0002-9440 [Print] United States
• PMID: 16877358 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ciliary Neurotrophic Factor
• Cytokines
• Mog protein, mouse
• Myelin Proteins
• Myelin-Associated Glycoprotein
• Myelin-Oligodendrocyte Glycoprotein
• RNA, Messenger

Topics

• Animals
• Axons (drug effects)
• Blood-Brain Barrier (drug effects, immunology)
• Cell Proliferation (drug effects)
• Ciliary Neurotrophic Factor (administration & dosage, pharmacokinetics, pharmacology, therapeutic use)
• Cytokines (genetics)
• Disease Models, Animal
• Encephalomyelitis, Autoimmune, Experimental (chemically induced)
• Inflammation (pathology)
• Injections, Intraperitoneal
• Mice
• Mice, Inbred C57BL
• Myelin Proteins
• Myelin-Associated Glycoprotein (immunology)
• Myelin-Oligodendrocyte Glycoprotein
• Oligodendroglia (cytology, drug effects, pathology)
• RNA, Messenger (genetics, metabolism)
• Spinal Cord (drug effects, immunology)
• T-Lymphocytes (cytology, drug effects, immunology)