Combined use of etanercept and MTX restores CD4+/CD8+ ratio and Tregs in spleen and thymus in collagen-induced arthritis
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To further explore the mechanism of etanercept (ENT, rhTNFR:Fc) and methotrexate (MTX) in the combined treatment of rheumatoid arthritis (RA), we investigated whether thymic and splenic T-cell subsets and their related cytokines imbalance could be restored by ETN/MTX treatment.
The effect of ETN/MTX on collagen-induced arthritis (CIA) was evaluated by arthritis scores, joint and spleen histopathology, as well as indices of thymus and spleen. T lymphocytes proliferation was determined by [3H]-TdR incorporation. Levels of TNF-α, LT-α, IL-1β, RANKL, IL-10, IL-17, IFN-γ and IL-6 were detected by enzyme linked immunosorbent assay. The subsets of T lymphocytes including CD4+, CD8+, CD3+CD4+, CD4+CD25+, CD4+CD62L+ and CD4+CD25+Foxp3+ cells were quantified using flow cytometry.
Combined administration of ETN/MTX significantly inhibited the proliferation of T lymphocytes, decreased serum IL-6, TNF-α, IL-1β, RANKL and macrophage supernatant IL-17, LT-α, increased serum IFN-γ and macrophage supernatant IL-10. Moreover, the combined administration could restore CD4+/CD8+ ratio and Treg cells of CIA thymus and spleen.
Taken together, our findings suggest that ENT/MTX may modify the abnormal T lymphocytes balance from central to peripheral lymphoid organs, which may partially, explained the mechanism of the combined administration.
KeywordsRheumatoid arthritis Collagen-induced arthritis T lymphocytes Immunological regulation Immunotherapy
This work was financially supported by the National Natural Science Foundation of China (30973543 and 81173075 to W. Wei), the Young Talents Foundation of the Education Department of Anhui Province (2010SQRL079 to Q. T. Wang), the Foundation from Janssen Research Council China (2011 to Q. T. Wang), the Anhui Provincial Natural Science Foundation (No. 1208085QH146 to QT Wang), and the Anhui Province Nature Science Foundation in University (KJ2011Z181, KJ2011Z180).
Conflict of interest
The authors declare that there are no conflicts of interest.
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