Effects of immunosuppressive treatment on interleukin-15 and interleukin-15 receptor α expression in muscle tissue of patients with polymyositis or dermatomyositis

Objectives: To investigate the expression of interleukin (IL)-15 and IL-15 receptor α (IL-15Rα) in muscle tissue from patients with polymyositis or dermatomyositis before and after conventional immunosuppressive (IS) treatment. Methods: Muscle biopsies from 17 patients before and after conventional IS treatment and seven healthy individuals were investigated by immunohistochemistry using antibodies against IL-15 and IL-15Rα. Quantification was performed by computerised image analysis. Cellular localisation of IL-15 was determined by double immunofluorescence. Clinical outcome was measured by the functional index and serum creatine kinase. Human myotubes were cultured and IL-15 staining was performed by immunocytochemistry. Results: IL-15 was observed in mononuclear inflammatory cells of muscle tissue while IL-15Rα was localised to mononuclear inflammatory cells, capillaries and large vessels. Double staining showed localisation of IL-15 to CD163+ macrophages. A significantly larger number of IL-15 and IL-15Rα-positive cells were seen in muscle tissue of patients compared with healthy individuals. Baseline IL-15 expression correlated negatively with improvement in muscle function. After conventional IS treatment, a significantly lower number of IL-15 and IL-15Rα-positive cells was found. However, compared with controls, eight of 17 patients still had more IL-15-positive cells and less muscle function improvement was shown in this group of patients, both in short-term and long-term observations. Human differentiated myotubes were negative for IL-15 staining. Conclusions: IL-15 and its receptor are expressed in the muscle tissue of patients with myositis and IL-15 expression is correlated with improvement in muscle function. IL-15 may play a role in the pathogenesis of myositis and could be a biological treatment target, at least in a subgroup of patients with polymyositis or dermatomyositis.