Combined use of etanercept and MTX restores CD4+/CD8+ ratio and Tregs in spleen and thymus in collagen-induced arthritis

B. Huang, Qingtong Wang, S. S. Song, Y. J. Wu, Y. K. Ma, L. L. Zhang, J. Y. Chen, H. X. Wu, L. Jiang, W. Wei

Research output: Contribution to journalArticle

24 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1229-1239
Number of pages11
JournalInflammation Research
Volume61
Issue number11
DOIs
StatePublished - Nov 1 2012
Externally publishedYes

Keywords

  • Collagen-induced arthritis
  • Immunological regulation
  • Immunotherapy
  • Rheumatoid arthritis
  • T lymphocytes

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

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    Huang, B., Wang, Q., Song, S. S., Wu, Y. J., Ma, Y. K., Zhang, L. L., Chen, J. Y., Wu, H. X., Jiang, L., & Wei, W. (2012). Combined use of etanercept and MTX restores CD4+/CD8+ ratio and Tregs in spleen and thymus in collagen-induced arthritis. Inflammation Research, 61(11), 1229-1239. https://doi.org/10.1007/s00011-012-0520-0