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

Objective-This study was performed to assess whether there is any change in the T cell cytokine pattern in early rheumatoid arthritis (RA) patients tr eated 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 wi th MTX for the cytokines tumour necrosis factor alpha (TNF alpha), interfer on gamma (IFN gamma), interleukin 4 (IL4) and interleukin 10 (IL10) by intr acellular staining of T cells derived from peripheral blood. Response to tr eatment was assessed by the modified disease activity score. Results-The clincial response was accompanied by a significant decrease of TNF alpha positive CD4(+) T cells from a median of 8.53% (interquartile ran ge 5.83-10.91%) before treatment to 6.17% (2.15-6.81%) after six to nine mo nths of treatment (p=0.021). Inversely, IL10 positive T cells increased fro m 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 INF gamma positive T cells and a small decrease of IL-4 positive T cells during treatment were observed. The percentage of IL4 positive CD4(+) T cells before treatment correlated with disease activ ity after six to nine months (r= -0.7066; p= 0.05). Conclusions-During treatment of RA with MTX the percentage of TNF alpha pro ducing T cells decreases whereas that of IL10 producing T cells increases. This may affect macrophage activation and, therefore, may represent a regul atory mechanism relevant to disease remission. Furthermore, the percentage of IL4 positive CD4(+) T cells at disease onset may be a useful prognostic marker.