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.

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.

• Authors: M Rudwaleit, Z Yin, S Siegert, M Grolms, A Radbruch, J Braun, J Sieper
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 59 Issue 4 Pg. 311-4 (Apr 2000) ISSN: 0003-4967 [Print] England
• PMID: 10733482 (Publication Type: Journal Article)

Chemical References

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

Topics

• Antirheumatic Agents (therapeutic use)
• Arthritis, Rheumatoid (drug therapy, 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)