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

Objective. To examine the effect of recombinant TSG-6 on collagen-induced a rthritis (CIA) in DBA/1J mice. TSG-6 is a tumor necrosis factor (TNF)/inter leukin-1 (IL-1)-inducible hyaluronan-binding protein produced by synovial c ells and chondrocytes that is present in synovial fluids of patients with r heumatoid arthritis. Methods, To determine the effect of TSG-6 on chronic inflammatory joint dis ease, we induced CIA in DBA/IJ mice by immunization with bovine type II col lagen. Animals were treated with 12 intraperitoneal doses of 200 mug of rec ombinant TSG-6, beginning 3 days before the expected onset of disease sympt oms. Progression of arthritis was monitored by determining the disease inci dence, arthritis index, and footpad swelling, Levels of IgG1, IgG2a, and Ig G2b antibodies against bovine and murine type II collagen and serum concent rations of IL-6 were determined at various time points. Histologic examinat ion of affected joints was performed similar to 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-t reated animals revealed little pannus formation and cartilage erosion, feat ures which were conspicuous in control mice. Animals treated with recombina nt TSG-6 developed significantly reduced levels of IgG1, IgG2a, and IgG2b a ntibodies against bovine and murine type IT collagen. Conclusion, The antiinflammatory effect of the TNF/IL-1-inducible TSG-6 pro tein in murine CIA suggests a role for this protein as an endogenous regula tor of the inflammatory process.