Soluble TNFR1 inhibits the development of experimental autoimmune neuritis by modulating blood-nerve-barrier permeability and inflammation.
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.
Taylor
Jude Matthew
JM
Neurology Laboratory, Department of Medicine (D06), University of Sydney, Australia. jtaylor@med.usyd.edu.au
Pollard
John David
JD
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
D000906:Antibodies; D047888:Receptors, Tumor Necrosis Factor, Type I