Soluble TNFR1 inhibits the development of experimental autoimmune neuritis by modulating blood–nerve-barrier permeability and inflammation
- 作者：Jude Matthew Taylor ; John David Pollard
- 关键词：EAN ; TNF ; Lymphotoxin ; Macrophage ; Demyelination ; Blood– ; nerve-barrier
- 刊名：Journal of Neuroimmunology
- 出版年：2007
- 期刊代码：32_01655728
- 类别：neu
- 出版时间：February 2007
- 卷：183
- 期：1-2
- 页码：118-124
- 文件大小：317 K
摘要
The role of TNFα/LTα 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). TNFα and LTα 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 TNFα and/or LTα 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.