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 w ith polymyositis (PM), inclusion body myositis (IBM), and dermatomyosi tis (DM). Methods. We performed indirect immunohistochemistry studies of muscle tissue sections with a panel of 16 different cytokine-specif ic 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 necros is 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 I BM and in 4 normal controls. Fresh frozen muscle tissue sections were fixed in formaldehyde before the procedure. The use of saponin as a de tergent to permeabilize the cell membranes enabled identification of i ntracellular cytokine production. Results. The most prominent Ending w as the expression of IL-1 alpha observed in all patients but in none o f the normal controls. In all patients with PM, DM, and IBM, IL-1 alph a was expressed in endothelial cells of capillaries, arterioles, and v enules in areas surrounded by inflammatory cells, and also in areas wi th 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 i n 10 of the 15 patients but, in contrast to IL-1 alpha, it was not exp ressed in blood vessel walls. TGF beta 1, TGF beta 2, and TGF beta 3 w ere strongly positive in all 15 patients, but only scattered cells wer e positive in the normal controls. The remaining cytokines were observ ed only in relatively few cells and only in occasional patients (altho ugh 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 wit h 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 p rocess in PM, IBM, and DM. A sustained, local release of T cell-derive d cytokines may not be a requirement for tissue injury in the inflamma tory myopathies. There does not appear to be a qualitative difference in cytokine expression patterns in PM, IBM, and DM.