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Ann Rheum Dis ; 71(6): 1055-63, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22267334

ABSTRACT

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.


Subject(s)
Dermatomyositis/drug therapy , Immunosuppressive Agents/therapeutic use , Interleukin-15 Receptor alpha Subunit/metabolism , Interleukin-15/metabolism , Muscle, Skeletal/drug effects , Polymyositis/drug therapy , Adult , Aged , Aged, 80 and over , Biopsy , Cohort Studies , Creatine Kinase/metabolism , Dermatomyositis/immunology , Dermatomyositis/pathology , Female , Humans , Interleukin-15/immunology , Interleukin-15 Receptor alpha Subunit/immunology , Macrophages/drug effects , Macrophages/immunology , Macrophages/metabolism , Male , Middle Aged , Muscle Fibers, Skeletal/drug effects , Muscle Fibers, Skeletal/immunology , Muscle Fibers, Skeletal/metabolism , Muscle, Skeletal/immunology , Muscle, Skeletal/pathology , Polymyositis/immunology , Polymyositis/pathology , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , T-Lymphocytes/metabolism
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