Journal Article

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

Zong, Mei, Loell, Ingela, McInnes, Iain B, Lundberg, Ingrid E, Alexanderson, Helene, Hallengren, Christina Ståhl, Lindroos, Eva, Nader, Gustavo A, Borg, Kristian, Arnardottir, Snjolaug

2012

Overview

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.

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,BMJ Publishing Group
• Subject: Adult / Aged / Aged, 80 and over / Antibodies / Biological and medical sciences / Biopsy / Capillaries / Cohort Studies / Creatine kinase / Creatine Kinase - metabolism / Dermatomyositis / Dermatomyositis - drug therapy / Dermatomyositis - immunology / Dermatomyositis - pathology / Diseases of the osteoarticular system / Female / Humans / Image processing / Immunocytochemistry / Immunofluorescence / Immunohistochemistry / Immunosuppressive Agents - therapeutic use / Inflammation / Interleukin 15 / Interleukin 15 receptors / Interleukin-15 - immunology / Interleukin-15 - metabolism / Interleukin-15 Receptor alpha Subunit - immunology / Interleukin-15 Receptor alpha Subunit - metabolism / Macrophages / Macrophages - drug effects / Macrophages - immunology / Macrophages - metabolism / Male / Medical sciences / Middle Aged / Muscle Fibers, Skeletal - drug effects / Muscle Fibers, Skeletal - immunology / Muscle Fibers, Skeletal - metabolism / Muscle, Skeletal - drug effects / Muscle, Skeletal - immunology / Muscle, Skeletal - pathology / Muscles / Myositis / Myotubes / Polymyositis / Polymyositis - drug therapy / Polymyositis - immunology / Polymyositis - pathology / Receptor mechanisms / Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis / T-Lymphocytes - drug effects / T-Lymphocytes - immunology / T-Lymphocytes - metabolism