title: Therapeutic inhibition of the alternative complement pathway attenuates chronic EAE.
abstract: Previous studies from our laboratory using complement-mutant mice demonstrated that the alternative pathway is the dominant activation pathway responsible for complement-mediated pathology in demyelinating disease. Using a well-characterized inhibitory monoclonal antibody (mAb 1379) directed against mouse factor B, we assessed the therapeutic value of inhibiting the alternative complement pathway in experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis. Administration of anti-factor B antibody to mice prior to the onset of clinical signs of active EAE had no affect on the onset or acute phase of disease, but significantly attenuated the chronic phase of disease resulting in reduced cellular infiltration, inflammation and demyelination in antibody-treated mice. Attenuation of the chronic phase of disease was long lasting even though antibody administration was terminated shortly after disease onset. Chronic disease was also attenuated in transferred EAE when anti-factor B antibody was administered before or after disease onset. Similar levels of disease attenuation were observed in transferred EAE using MOG-specific encephalitogenic T cells. These studies demonstrate the therapeutic potential for inhibition of factor B in the chronic phase of demyelinating disease, where treatment options are limited.
authors: Department of Microbiology, University of Alabama at Birmingham, 845 19th St. S., Birmingham, AL 35294, USA.
authors: Xianzhen
authors: X
authors: Hu
authors: V Michael
authors: VM
authors: Holers
authors: Joshua M
authors: JM
authors: Thurman
authors: Trent R
authors: TR
authors: Schoeb
authors: Theresa N
authors: TN
authors: Ramos
authors: Scott R
authors: SR
authors: Barnum
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology*; D011415:Complement Factor B / Q000145:classification; D003170:Complement Pathway, Alternative / Q000187:drug effects* / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology*; D003711:Demyelinating Diseases / Q000276:immunology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D003165:Complement System Proteins; D011415:Complement Factor B