TY - JOUR T1 - Influence of longterm therapy with methotrexate and low dose corticosteroids on type 1 and type 2 cytokine production in CD4+ and CD8+ T lymphocytes of patients with rheumatoid arthritis. JF - The Journal of Rheumatology JO - J Rheumatol SP - 1793 LP - 1799 VL - 28 IS - 8 AU - A J Schuerwegh AU - J F van Offel AU - C H Bridts AU - W J Stevens AU - L S De Clerck Y1 - 2001/08/01 UR - http://www.jrheum.org/content/28/8/1793.abstract N2 - OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease with predominance of type I cytokine [interleukin 2 (IL-2), interferon-gamma (IFN-gamma)] production. In this prospective study, we evaluated the influence 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 intracellular 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 showed 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 positive CD4+ T cells and IFN-gamma positive CD4+ and CD8+ T lymphocytes was observed (p = 0.0003, p = 0.0007, p = 0.001). The percentage of IL-4/IFN-gamma positive CD4+ and CD8+ T cells was significantly higher after 12 months of therapy (p = 0.01, p = 0.02). There was a positive correlation between the percentage 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: Longterm therapy with MTX in combination with low dose corticosteroids for RA influenced the predominance of type 1 cytokines toward normalization of the cytokine balance in both CD4+ and CD8+ T lymphocytes. ER -