title: 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.affiliation: Neurology Laboratory, Department of Medicine (D06), University of Sydney, Australia. jtaylor@med.usyd.edu.au
authors.forename: Jude Matthew
authors.initials: JM
authors.lastname: Taylor
authors.forename: John David
authors.initials: JD
authors.lastname: Pollard
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000097:blood; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000503:physiopathology; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000150:complications* / Q000473:pathology*; D005260:Female; D007249:Inflammation / Q000209:etiology* / Q000517:prevention & control*; D008264:Macrophages / Q000187:drug effects; D008297:Male; D009186:Myelin Sheath / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000008:administration & dosage*; D013997:Time Factors
chemical_list: D000906:Antibodies; D047888:Receptors, Tumor Necrosis Factor, Type I