Methotrexate/corticosteroid therapy for arthritis modulates cytokine profiles

WESTPORT, CT (Reuters Health) – Long-term treatment of rheumatoid arthritis with the combination of methotrexate and low-dose corticosteroids is associated with a normalization of cytokine balance, Belgian researchers report.

Dr. Luc S. De Clerck and colleagues from the University of Antwerp describe their study in the August issue of The Journal of Rheumatology. "Rheumatoid arthritis is predominantly a Th1 disease," Dr. De Clerck explained to Reuters Health. The production of inflammatory T-helper-1 cytokines, such as interleukin-2 (IL-2) and interferon-gamma, in T lymphocytes plays a pivotal role in the perpetuation of joint inflammation, while Th2 cytokines like interleukin-4 can have anti-inflammatory effects in rheumatoid arthritis.

In this prospective study, the team isolated peripheral blood mononuclear cells from 10 control subjects and 20 RA subjects before and 12 months after methotrexate/low dose corticosteroid therapy.

They found that the combined treatment led to a decrease in the production of pro-inflammatory Th1 cytokines. Before therapy, rheumatoid arthritis patients had increased levels of IL-2 positive CD4+ and CD8+ T cells (p = 0.002, p = 0.01, respectively) and interferon-gamma positive CD8+ T cells (p = 0.0006), compared with controls. These levels dropped "significantly" after 12 months of therapy, leading to "a normalized balance between type 1 and type 2 cytokines."

According to Dr. De Clerck and colleagues, "a positive correlation between the percentage of interferon-gamma positive CD4+ T cells and disease activity" also emerged.

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