Response to methotrexate in early rheumatoid arthritis is associated with a decrease of T cell derived tumour necrosis factor α, 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 α (TNFα), interferon γ (IFNγ), 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 TNFα 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 INFγ 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 TNFα 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.