title: Effects of immunosuppressive treatment on interleukin-15 and interleukin-15 receptor α expression in muscle tissue of patients with polymyositis or dermatomyositis.
abstract: OBJECTIVE
  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.
authors.affiliation: Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden. mei.zong@ki.se
authors.forename: Mei
authors.initials: M
authors.lastname: Zong
authors.forename: Ingela
authors.initials: I
authors.lastname: Loell
authors.forename: Eva
authors.initials: E
authors.lastname: Lindroos
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: Nader
authors.forename: Helene
authors.initials: H
authors.lastname: Alexanderson
authors.forename: Christina Ståhl
authors.initials: CS
authors.lastname: Hallengren
authors.forename: Kristian
authors.initials: K
authors.lastname: Borg
authors.forename: Snjolaug
authors.initials: S
authors.lastname: Arnardottir
authors.forename: Iain B
authors.initials: IB
authors.lastname: McInnes
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Lundberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D015331:Cohort Studies; D003402:Creatine Kinase / Q000378:metabolism; D003882:Dermatomyositis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D019409:Interleukin-15 / Q000276:immunology / Q000378:metabolism*; D053720:Interleukin-15 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D017285:Polymyositis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: C569274:IL15 protein, human; D007166:Immunosuppressive Agents; D019409:Interleukin-15; D053720:Interleukin-15 Receptor alpha Subunit; D003402:Creatine Kinase