Comparative efficacy of TACI-Ig with TNF-alpha inhibitor and methotrexate in DBA/1 mice with collagen-induced arthritis.

Abstract: The efficacies of TACI-Ig, rhTNFR:Fc and Methotrexate were compared in collagen-induced arthritis (CIA) mice. Sixty animals were divided into six groups: TACI-Ig (9mg/kg), rhTNFR:Fc (4mg/kg), Methotrexate (2mg/kg) and IgG-Fc (9mg/kg) groups and were given medication for six weeks. Meanwhile, normal and CIA mice were given as control. The different efficacies of drugs were evaluated by the analyses of ankle joints and spleens pathology, cytokines, T and B lymphocytes subsets. TACI-Ig and rhTNFR:Fc reduced arthritis scores seven days later than that of Methotrexate. TACI-Ig and Methotrexate were superior to rhTNFR:Fc in reduction synovial hyperplasia and cell infiltration scores. The same result was observed for scores of spleens histopathology. TACI-Ig and Methotrexate presented higher efficacy than rhTNFR:Fc on B lymphocyte stimulator, but TACI-Ig was inferior to rhTNFR:Fc on TNF-alpha. TACI-Ig and Methotrexate could reduce significantly IgA and IgM, but rhTNFR:Fc had no effects on these immunoglobulins. TACI-Ig had more efficacy than rhTNFR:Fc in the decrease of CD4+CD154+ T cell. TACI-Ig and Methotrexate also reduced CD4+CD69+ T cell, rhTNFR:Fc had no effects on the T cell subset. TACI-Ig and Methotrexate were superior to rhTNFR:Fc on CD4+CD62L+T cells. TACI-Ig and Methotrexate could reduce CD19+IgD+ and CD19+CD21+ B cells, but rhTNFR:Fc had no obvious effect on above B cells subsets. TACI-Ig is as effective as rhTNFR:Fc and Methotrexate on CIA mice by ameliorating joint and spleen pathology, regulating T and B lymphocytes function, although different mechanisms among them. This study would be useful for treatment selection of rheumatoid arthritis in different pathological conditions. [Copyright &y& Elsevier]