ATTENUATION OF COLLAGEN-INDUCED ARTHRITIS IN 55-KDA TNF RECEPTOR-TYPE-1 (TNFR1)-IGG1-TREATED AND TNFR1-DEFICIENT MICE

The role of TNF and its type 1 receptor (TNFR1) in the pathogenesis of collagen-induced arthritis (CIA) was investigated in mice using two a pproaches, First, DBA/1 mice were treated after immunization with type II collagen by injecting TNFR1-IgG1 fusion protein to neutralize syst emic TNF, CIA was prevented when treatment was administered shortly be fore the onset of clinical disease, suggesting that TNF is a crucial m ediator in the late initiation phase of the arthritic process, In a se cond approach, TNFR1-deficient mice, generated by gene targeting and c rossed to DBA/1, were used, These mice developed CIA with a low incide nce and in a milder form, However, once a joint was afflicted, the dis ease progressed in this joint to the same end stage as that in wild-ty pe mice, These data suggest that TNFR1 is the main transducer of TNF p roinflammatory effects establishing CIA, but the progression of arthri tis to tissue destruction and ankylosis is independent of TNFR1.