Erschienen in:
01.11.2012 | Original Research Paper
Combined use of etanercept and MTX restores CD4+/CD8+ ratio and Tregs in spleen and thymus in collagen-induced arthritis
verfasst von:
B. Huang, Q. T. Wang, S. S. Song, Y. J. Wu, Y. K. Ma, L. L. Zhang, J. Y. Chen, H. X. Wu, L. Jiang, W. Wei
Erschienen in:
Inflammation Research
|
Ausgabe 11/2012
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Abstract
Objective
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.
Methods
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.
Results
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.
Conclusion
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.