Skip to main content

Advertisement

Log in

The effects of adalimumab and methotrexate treatment on peripheral Th17 cells and IL-17/IL-6 secretion in rheumatoid arthritis patients

  • Original Article
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

Objective of the study is to assess the effects of adalimumab and MTX therapy on peripheral Th17 cells and IL-17/IL-6 secretion in RA patients. Twenty active RA patients were treated with oral MTX 15 mg per week (MTX group, n = 10), or hypodermal adalimumab 40 or 80 mg every other week (ADA group, n = 10). Peripheral blood samples were taken for laboratory evaluation at week 0 and week 12 of treatment, including flowcytometric detection of peripheral CD4(+) IL-17(+) cells, RT-PCR detection of mRNA expressions of IL-17, RORc and FoxP3, and ELISA determination of serum IL-17 and IL-6. Ten age and sex marched healthy volunteers were included as normal controls. Results showed that (1) DAS28 in both groups improved at week 12 compared to week 0 (3.9 ± 1.3 vs. 6.4 ± 1.4 and 3.2 ± 0.9 vs. 5.2 ± 0.9, respectively). (2) The percentage and MFI of peripheral CD4(+) IL-17(+) cells in RA patients were significantly higher comparing to normal controls (1.64 ± 0.97% vs. 0.75 ± 0.20%, p < 0.01; and 29.8 ± 9.7 vs. 19.8 ± 4.6, p < 0.05, respectively), and positively correlated with ESR and DAS28. Peripheral Th17 cells and serum IL-6 in RA patients decreased after treatment (from 1.60 ± 0.78% to 1.28 ± 0.41%, and from 17.15 ± 14.53 pg/ml to 6.97 ± 5.51 pg/ml, p < 0.05, respectively). Peripheral FoxP3 mRNA expression in active RA patients was significantly lower comparing to normal controls, and negatively correlated with ESR. Baseline Th17 percentage of RA patients negatively correlated with DAS28 improvement after treatment. In conclusion, adalimumab and MTX treatment down regulates peripheral Th17 cells and serum IL-6 level in RA patients. Baseline Th17 level negatively predicts the effect of adalimumb/MTX treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Steinman L (2007) A brief history of TH17, the first major revision in the TH1/TH2 hypothesis of T cell–mediated tissue damage. Nature Med 13:139–145

    Article  CAS  PubMed  Google Scholar 

  2. Londei M (2005) Role of regulatory T cells in experimental arthritis and implications for clinical use. Arthritis Res Ther 7:118–120

    Article  CAS  PubMed  Google Scholar 

  3. Weaver CT, Harrington LE, Mangan PR, Gavrieli M, Murphy KM (2006) Th17: an effector CD4 T cell lineage with regulatory T cell ties. Immunity 24:677–688

    Article  CAS  PubMed  Google Scholar 

  4. Pene J, Chevalier S, Preisser L, Venereau E, Guilleux MH, Ghannam S et al (2008) Chronically inflamed human tissues are infiltrated by highly differentiated Th17 lymphocytes. J Immunol 180:7423–7430

    CAS  PubMed  Google Scholar 

  5. McInnes IB, Liew FY (2005) Cytokine networks—towards new therapies for rheumatoid arthritis. Nat Clin Pract Rheumatol 1:31–39

    Article  CAS  PubMed  Google Scholar 

  6. Lundy SK, Sarkar S, Tesmer LA, Fox DA (2007) Cells of the synovium in rheumatoid arthritis. T lymphocytes. Arthritis Res Ther 9:202

    Article  PubMed  Google Scholar 

  7. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324

    Article  CAS  PubMed  Google Scholar 

  8. Prevoo ML, van’t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL et al (1995) Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 38:44–48

    Article  CAS  PubMed  Google Scholar 

  9. Kanof ME, Smith PD, Zola H (2001) Isolation of whole mononuclear cells from peripheral blood and cord blood. Curr Protoc Immunol chap 7:unit 7.1

  10. Kuligowska M, Odrowaz-Sypniewska G (2004) Role of interleukin-17 in cartilage and bone destruction in rheumatoid arthritis. Ortop Traumtol Rehabil 6:235–241

    Google Scholar 

  11. Sutton C, Brereton C, Keogh B, Mills KH, Lavelle EC (2006) A crucial role for interleukin (IL)-1 in the induction of IL-17-producing T cells that mediate autoimmune encephalomyelitis. J Exp Med 03:1685–1691

    Article  Google Scholar 

  12. Chen Z, Laurence A, O’Shea JJ (2007) Signal transduction pathways and transcriptional regulation in the control of Th17 differentiation. Semin Immunol 19:400–408

    Article  CAS  PubMed  Google Scholar 

  13. Williams RO, Paleolog E, Feldmann M (2007) Cytokine inhibitors in rheumatoid arthritis and other autoimmune diseases. Curr Opin Pharmacol 7:412–417

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was partly supported by New Century Excellent Talents, Ministry of Education of China (NCET-04-0191), National Natural Sciences Foundation of China (30400410), and National Program for Key Basic Research Project (2007CB512405 for Immunology), Ministry of Science and Technology, China.

Conflict of interest statement

The author(s) declare that they have no competing interests.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Fengchun Zhang or Xuan Zhang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yue, C., You, X., Zhao, L. et al. The effects of adalimumab and methotrexate treatment on peripheral Th17 cells and IL-17/IL-6 secretion in rheumatoid arthritis patients. Rheumatol Int 30, 1553–1557 (2010). https://doi.org/10.1007/s00296-009-1179-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-009-1179-x

Keywords

Navigation