Influence of longterm therapy with methotrexate and low dose corticosteroids on type 1 and type 2 cytokine production in CD4+and CD8+T lymphocytes ofpatients with rheumatoid arthritis

Objective. Rheumatoid arthritis (RA) is a chronic inflammatory disease with predominance of type 1 cytokine [interleukin 2 (IL-2), interferon-gamma (I FN-gamma)] production. In this prospective study, we evaluated the influenc e of longterm therapy with methotrexate (MTX) in combination with low dose corticosteroids on the type 1/type 2 cytokine balance in RA. Methods. Peripheral blood mononuclear cells were isolated from 10 controls and 20 patients with RA before therapy and after 12 mo of therapy with MTX in combination with low dose corticosteroids. Using flow cytometry, the int racellular production of IL-2, IFN-gamma and IL-4 was measured in CD4+ and CD8+ T lymphocytes. Results. Compared with healthy controls, patients with RA before therapy sh owed an increased percentage of IL-2 positive CD4+ and CD8+ T cells (p = 0. 002, p = 0.01, respectively). An increased percentage of IFN-gamma positive CD8+ T cells was found (p = 0.0006) compared with the control group. After 12 months of therapy, a significantly decreased percentage of IL-2 positiv e CD4+ T cells and IFN-gamma positive CD4+ and CD8+ T lymphocytes was obser ved (p = 0.0003, p = 0.0007, p = 0.001). The percentage of IL-4/IFN-gamma p ositive CD4+ and CD8+ T cells was significantly higher after 12 months of t herapy (p = 0.01, p = 0.02). There was a positive correlation between the p ercentage of IFN-gamma positive CD4+ T cells and disease activity variables (Ritchie Index and number of swollen joints) in RA patients before therapy (r = 0.6, p = 0.04 and r = 0.4, p = 0.05). Conclusion. Lon.-term therapy with MTX in combination with low dose cortico steroids for RA influenced the predominance of type 1 cytokines toward norm alization of the cytokine balance in both CD4+ and CD8+ T lymphocytes.