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

21 Citations (Scopus)

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

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CD4-CD8 Ratio
Experimental Arthritis
Methotrexate
Thymus Gland
Spleen
Interleukin-17
T-Lymphocyte Subsets
T-Lymphocytes
Interleukin-1
Interleukin-10
Interleukin-6
Macrophages
Regulatory T-Lymphocytes
Serum
Arthritis
Rheumatoid Arthritis
Flow Cytometry
Joints
Enzyme-Linked Immunosorbent Assay
Etanercept

Keywords

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

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

Cite this

Combined use of etanercept and MTX restores CD4+/CD8+ ratio and Tregs in spleen and thymus in collagen-induced arthritis. / Huang, B.; Wang, Qingtong; Song, S. S.; Wu, Y. J.; Ma, Y. K.; Zhang, L. L.; Chen, J. Y.; Wu, H. X.; Jiang, L.; Wei, W.

In: Inflammation Research, Vol. 61, No. 11, 01.11.2012, p. 1229-1239.

Research output: Contribution to journalArticle

Huang, B, Wang, Q, Song, SS, Wu, YJ, Ma, YK, Zhang, LL, Chen, JY, Wu, HX, 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, vol. 61, no. 11, pp. 1229-1239. https://doi.org/10.1007/s00011-012-0520-0
Huang, B. ; Wang, Qingtong ; Song, S. S. ; Wu, Y. J. ; Ma, Y. K. ; Zhang, L. L. ; Chen, J. Y. ; Wu, H. X. ; Jiang, L. ; Wei, W. / Combined use of etanercept and MTX restores CD4+/CD8+ ratio and Tregs in spleen and thymus in collagen-induced arthritis. In: Inflammation Research. 2012 ; Vol. 61, No. 11. pp. 1229-1239.
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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.",
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T1 - Combined use of etanercept and MTX restores CD4+/CD8+ ratio and Tregs in spleen and thymus in collagen-induced arthritis

AU - Huang, B.

AU - Wang, Qingtong

AU - Song, S. S.

AU - Wu, Y. J.

AU - Ma, Y. K.

AU - Zhang, L. L.

AU - Chen, J. Y.

AU - Wu, H. X.

AU - Jiang, L.

AU - Wei, W.

PY - 2012/11/1

Y1 - 2012/11/1

N2 - 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.

AB - 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.

KW - Collagen-induced arthritis

KW - Immunological regulation

KW - Immunotherapy

KW - Rheumatoid arthritis

KW - T lymphocytes

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