Amelioration of collagen-induced arthritis in DBA/1J mice by recombinant TSG-6, a tumor necrosis factor/interleukin-1-inducible protein

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Abstract
Objective To examine the effect of recombinant TSG‐6 on collagen‐induced arthritis (CIA) in DBA/1J mice. TSG‐6 is a tumor necrosis factor (TNF)/interleukin‐1 (IL‐1)–inducible hyaluronan‐binding protein produced by synovial cells and chondrocytes that is present in synovial fluids of patients with rheumatoid arthritis. Methods To determine the effect of TSG‐6 on chronic inflammatory joint disease, we induced CIA in DBA/1J mice by immunization with bovine type II collagen. Animals were treated with 12 intraperitoneal doses of 200 μg of recombinant TSG‐6, beginning 3 days before the expected onset of disease symptoms. Progression of arthritis was monitored by determining the disease incidence, arthritis index, and footpad swelling. Levels of IgG1, IgG2a, and IgG2b antibodies against bovine and murine type II collagen and serum concentrations of IL‐6 were determined at various time points. Histologic examination of affected joints was performed ∼20 days after the onset of arthritis. Results Treatment with recombinant TSG‐6 protein had a potent ameliorative effect, manifested by decreases in the disease incidence, arthritis index, and footpad swelling. Histologic examination of affected joints in TSG‐6–treated animals revealed little pannus formation and cartilage erosion, features which were conspicuous in control mice. Animals treated with recombinant TSG‐6 developed significantly reduced levels of IgG1, IgG2a, and IgG2b antibodies against bovine and murine type II collagen. Conclusion The antiinflammatory effect of the TNF/IL‐1–inducible TSG‐6 protein in murine CIA suggests a role for this protein as an endogenous regulator of the inflammatory process.