Soluble TNFR1 inhibits the development of experimental autoimmune neuritis by modulating blood-nerve-barrier permeability and inflammation.

Abstract

The role of TNFalpha/LTalpha during EAN induced by active immunization with peripheral nerve myelin was examined by administering a recombinant soluble chimeric form of human TNF receptor 1 (TNFR1-IgG). TNFalpha and LTalpha do not directly contribute to neurological deficit during EAN since treatment with TNFR1-IgG after onset failed to alter the course of disease. Prophylaxis with a single dose of TNFR1-IgG delayed the onset of EAN and was accompanied initially by inhibition of blood-nerve-barrier permeability and inflammation. Subsequently, the number of infiltrating macrophages and blood-nerve-barrier permeability increased but the disease symptoms remained mild for five days (on average a limp tail) after which severe EAN developed. The antibody titer to peripheral nerve myelin was unaltered by prophylaxis with TNFR1-IgG. The markedly altered tempo of disease onset after TNFR1-IgG prophylaxis indicates that TNFalpha and/or LTalpha have a key role in the development of blood-nerve-barrier permeability and the coupling of macrophage activation and recruitment to peripheral nerve pathology during EAN.

• Authors: Jude Matthew Taylor, John David Pollard
• Journal: Journal of neuroimmunology (J Neuroimmunol) Vol. 183 Issue 1-2 Pg. 118-24 (Feb 2007) ISSN: 0165-5728 [Print] Netherlands
• PMID: 17196669 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies
• Receptors, Tumor Necrosis Factor, Type I

Topics

• Animals
• Antibodies (administration & dosage, blood)
• Blood-Brain Barrier (drug effects, physiopathology)
• Capillary Permeability (drug effects, physiology)
• Disease Models, Animal
• Encephalomyelitis, Autoimmune, Experimental (chemically induced, complications, pathology)
• Female
• Inflammation (etiology, prevention & control)
• Macrophages (drug effects)
• Male
• Myelin Sheath (immunology)
• Rats
• Rats, Inbred Lew
• Receptors, Tumor Necrosis Factor, Type I (administration & dosage)
• Time Factors