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 approaches. First, DBA/1 mice were treated after immunization with type II collagen by injecting TNFR1-IgG1 fusion protein to neutralize systemic TNF. CIA was prevented when treatment was administered shortly before the onset of clinical disease, suggesting that TNF is a crucial mediator in the late initiation phase of the arthritic process. In a second approach, TNFR1-deficient mice, generated by gene targeting and crossed to DBA/1, were used. These mice developed CIA with a low incidence and in a milder form. However, once a joint was afflicted, the disease progressed in this joint to the same end stage as that in wild-type mice. These data suggest that TNFR1 is the main transducer of TNF proinflammatory effects establishing CIA, but the progression of arthritis to tissue destruction and ankylosis is independent of TNFR1.
Mori
L
L
Department of Research, University Hospital, Basel, Switzerland.
Iselin
S
S
De Libero
G
G
Lesslauer
W
W
D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001168:Arthritis / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D001172:Arthritis, Rheumatoid; D001483:Base Sequence; D002678:Chimera; D003094:Collagen / Q000276:immunology*; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D018450:Disease Progression; D004198:Disease Susceptibility; D018390:Gene Targeting; D007114:Immunization; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology*; D007143:Immunoglobulin Heavy Chains / Q000276:immunology / Q000378:metabolism*; D007142:Immunoglobulin gamma-Chains; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D015703:Antigens, CD; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007142:Immunoglobulin gamma-Chains; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; C099374:Ro 45-2081; D003094:Collagen