Response to methotrexate in early rheumatoid arthritis is associated with a decrease of T cell derived tumour necrosis factor alpha, increase of interleukin 10, and predicted by the initial concentration of interleukin 4

Ann Rheum Dis. 2000 Apr;59(4):311-4. doi: 10.1136/ard.59.4.311.

Abstract

Objective: This study was performed to assess whether there is any change in the T cell cytokine pattern in early rheumatoid arthritis (RA) patients treated with methotrexate (MTX) and whether the lymphocytic cytokine pattern correlates with disease activity.

Methods: Eight patients with RA (disease duration < six months) were studied serially before, after three, and after six to nine months of treatment with MTX for the cytokines tumour necrosis factor alpha (TNFalpha), interferon gamma (IFNgamma), interleukin 4 (IL4) and interleukin 10 (IL10) by intracellular staining of T cells derived from peripheral blood. Response to treatment was assessed by the modified disease activitiy score.

Results: The clincial response was accompanied by a significant decrease of TNFalpha positive CD4(+) T cells from a median of 8.53% (interquartile range 5.83-10.91%) before treatment to 6.17% (2.15-6.81%) after six to nine months of treatment (p=0.021). Inversely, IL10 positive T cells increased from a median of 0.65% (interquartile range 0.6-0.93%) to a median of 1. 3% (1.22%-1.58%) after six to nine months of treatment (p=0.009). No significant change in the percentage of INFgamma positive T cells and a small decrease of IL4 positive T cells during treatment were observed. The percentage of IL4 positive CD4(+) T cells before treatment correlated with disease activity after six to nine months (r= -0.7066; p=0.05).

Conclusions: During treatment of RA with MTX the percentage of TNFalpha producing T cells decreases whereas that of IL10 producing T cells increases. This may affect macrophage activation and, therefore, may represent a regulatory mechanism relevant to disease remission. Furthermore, the percentage of IL4 positive CD4(+) T cells at disease onset may be a useful prognostic marker.

MeSH terms

  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Biomarkers / analysis
  • CD4-Positive T-Lymphocytes / immunology
  • Cytokines / metabolism*
  • Flow Cytometry
  • Humans
  • Interleukin-10 / metabolism
  • Interleukin-4 / metabolism
  • Methotrexate / therapeutic use*
  • Prognosis
  • Prospective Studies
  • T-Lymphocyte Subsets / immunology*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antirheumatic Agents
  • Biomarkers
  • Cytokines
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-4
  • Methotrexate