The effects of adalimumab and methotrexate treatment on peripheral Th17 cells and IL-17/IL-6 secretion in rheumatoid arthritis patients
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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.
KeywordsRheumatoid arthritis Adalimumab Th17 Interleukin-17 Interleukin-6
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.
- 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 38:44–48CrossRefPubMedGoogle 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 7.1Google Scholar
- 10.Kuligowska M, Odrowaz-Sypniewska G (2004) Role of interleukin-17 in cartilage and bone destruction in rheumatoid arthritis. Ortop Traumtol Rehabil 6:235–241Google Scholar