Cytokine production in muscle tissue of patients with idiopathic inflammatory myopathies

Objective. To study cytokine expression in muscle tissues of patients with inflammatory myopathies and to compare the profiles of patients with polymyositis (PM), inclusion body myositis (IBM), and dermatomyositis (DM). Methods. We performed indirect immunohistochemistry studies of muscle tissue sections with a panel of 16 different cytokine-specific monoclonal antibodies, directed against interleukin-1 alpha, (IL-1 alpha), IL-1 beta, IL-1 receptor antagonist (IL-1Ra), IL-2, IL-3, IL-4, IL-6, IL-8, IL-10, IL-13, interferon-gamma (IFN gamma), tumor necrosis factor alpha (TNF alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), transforming growth factor beta 1 (TGF beta 1), TGF beta 2, and TGF beta 3 in 5 untreated patients each with PM, DM, and IBM and in 4 normal controls. Fresh frozen muscle tissue sections were fixed in formaldehyde before the procedure. The use of saponin as a detergent to permeabilize the cell membranes enabled identification of intracellular cytokine production. Results. The most prominent Ending was the expression of IL-1 alpha observed in all patients but in none of the normal controls. In all patients with PM, DM, and IBM, IL-1 alpha was expressed in endothelial cells of capillaries, arterioles, and venules in areas surrounded by inflammatory cells, and also in areas with no or scarce inflammatory cells in both endomysium and perimysium. Furthermore, IL-1 alpha was also expressed in mononuclear inflammatory cells in all 15 cases. IL-1 beta was observed in inflammatory cells in 10 of the 15 patients but, in contrast to IL-1 alpha, it was not expressed in blood vessel walls. TGF beta 1, TGF beta 2, and TGF beta 3 were strongly positive in all 15 patients, but only scattered cells were positive in the normal controls. The remaining cytokines were observed only in relatively few cells and only in occasional patients (although the patients were selected far the presence of large infiltrates), and in none of the controls. The patterns were similar in PM, DM, and IBM. Conclusion. Cytokine expression in muscle tissue of patients with inflammatory myopathy is dominated by IL-1 alpha, IL-1 beta, and TGF beta 1-3. The predominant IL-1 alpha expression in the blood vessels indicates an importance of the endothelial cells in the inflammatory process in PM, IBM, and DM. A sustained, local release of T cell-derived cytokines may not be a requirement for tissue injury in the inflammatory myopathies. There does not appear to be a qualitative difference in cytokine expression patterns in PM, IBM, and DM.