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Methotrexate Alters T-Cell Cytokine Patterns in Patients With Rheumatoid Arthritis

WESTPORT, Apr 18 (Reuters Health) - After 6 to 9 months of treatment of rheumatoid arthritis with methotrexate, the proportion of tumor necrosis factor (TNF)-alpha-positive T cells in the peripheral blood declines significantly, while the number of interleukin (IL)-10-positive T cells increases significantly.

"This may affect macrophage activation and, therefore, may represent a regulatory mechanism relevant to disease remission," Dr. Joachim Sieper, of Deutsches Rheuma-Forschungszentrum in Berlin, Germany, and colleagues say in the April issue of Annals of Rheumatic Disease.

The investigators measured the levels of T-cell cytokines in the
peripheral blood of eight patients with rheumatoid arthritis, disease
duration less then 6 months, before treatment with methotrexate, after 3 months and after 6 to 9 months. They looked at TNF-alpha, IL-10, IL-4 and interferon-gamma.

The number of TNF-alpha-positive CD4 T cells decreased significantly, from a median of 8.53% at baseline to 6.17% after 6 to 9 months of treatment. At the same time, levels of IL-10-positive T cells
increased significantly in the peripheral blood of patients, from a
median of 0.65% to 1.3%.

From these data, it cannot be determined if the changes in TNF-alpha and IL-10 are independent or dependent events, Dr. Sieper and colleagues say. It also remains unclear, they add, if the drop in TNF-alpha is a primary event in disease remission or is secondary to disease remission.

Levels of the other cytokines measured did not change significantly
during treatment. However, baseline levels of IL-4-positive T cells in
peripheral blood were significantly correlated with disease activity at
6 to 9 months after treatment with methotrexate. The percentage of
IL-4-positive CD4 T cells at disease onset may, therefore, "be a
useful prognostic marker," the authors conclude.

Ann Rheum Dis 2000;59:311-314.

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