Patients with myositis may respond to anakinra. Extramuscular score, muscle CD163 macrophages and IL-1α expression, blood CD4 activated/memory T cells might associate with anakinra treatment response. Blocking the IL-1 receptor disfavoured Th17 cell differentiation both in vivo and in vitro.

Objectives: To determine whether muscle weakness is correlated with inflammation, expression of interleukin 1a (IL1a) and major histocompatibility complex (MHC) class I and II antigens on muscle fibres. Methods: Biopsy specimens from clinically symptomatic (proximal muscles) and asymptomatic (all distal but two proximal) muscles in eight patients with polymyositis, three patients with dermatomyositis and six healthy controls were analysed by immunohistochemistry for the presence of T cells and macrophages, and expression of IL1a and of MHC class I and II antigens. Results were evaluated by conventional light microscopy and by computerised image analysis. Results: Inflammatory infiltrates with T cells and macrophages were observed to an equal degree in both symptomatic and asymptomatic muscle. The numbers of capillaries with IL1a expression were significantly higher (p,0.05) in the symptomatic and asymptomatic muscles of patients than in controls. The total IL1a expression per tissue section assessed by computerised image analysis was significantly higher in symptomatic muscles but not in asymptomatic muscles compared with that in controls. Neither the number of IL1a-positive capillaries nor the total IL1a expression differed significantly between symptomatic and asymptomatic muscles. Expression of MHC class I and II antigens on muscle fibres was detected in both symptomatic and asymptomatic muscles but rarely in healthy controls. Conclusions: Presence of inflammatory infiltrates, T cells and macrophages, and expression of MHC class I and II antigens and of IL1a on muscle fibres were independent of clinical symptoms, and were present to an equal degree in both proximal and distal muscles. Thus, other factors seem to determine the development of clinical symptoms. One such factor could be variations in physical demands.

Objective. Interleukin-1 (IL-1) acts via its receptors to induce gene expression that mediates protein synthesis involved in inflammation. Increased expression of IL-1␣ and IL-1␤ in muscle tissue from patients with polymyositis and dermatomyositis has been demonstrated. It is not known whether the reciprocal IL-1 receptors are expressed in human muscle tissue. The purpose of this study was to investigate the expression of IL-1 receptors and their ligands in muscle tissue from patients with myositis and from healthy controls.Methods. Muscle biopsy tissues from 10 patients with polymyositis or dermatomyositis and 7 healthy control subjects were investigated by immunohistochemistry using antibodies against IL-1 receptor type I (IL-1RI), IL-1RII, IL-1␣, IL-1␤, and IL-1 receptor antagonist (IL-1Ra). Quantification was performed by computerized image analysis, and localization of expression was determined by double staining using immunofluorescence and confocal microscopy.Results. In tissue samples from the patients, IL-1RI and IL-1RII were expressed in muscle fibers, inflammatory cells, and endothelial cells. Expression in muscle fibers was localized to the sarcolemma and nuclei. IL-1␣ was expressed in endothelial cells and inflammatory cells, whereas IL-1␤ and IL-1Ra were expressed only in inflammatory cells. Expression of the two IL-1 receptors and their ligands was significantly higher in patients than in controls. IL-1 receptor expression on muscle fibers was most pronounced in the vicinity of cells expressing IL-1␣ and IL-1␤.Conclusion. The increased expression of IL-1 receptor and the colocalization with reciprocal ligands in patients with myositis but not in healthy controls support the hypothesis of a crucial role of IL-1 in the pathogenesis of polymyositis and dermatomyositis.

Objectives:To investigate the expression of microsomal prostaglandin E (PGE) synthase 1 (mPGES-1) and cyclooxygenase (COX) in muscle biopsies from patients with polymyositis or dermatomyositis before and after conventional immunosuppressive treatment.Methods:mPGES-1 and COX expression was evaluated by immunohistochemistry in muscle tissue from healthy individuals and from patients with polymyositis or dermatomyositis before and after conventional immunosuppressive treatment. The number of inflammatory cell infiltrates, T lymphocytes and macrophages was estimated before and after treatment. To localise the mPGES-1 expression double immunofluorescence was performed with antibodies against mPGES-1, CD3, CD68, CD163 and a fibroblast marker. A functional index was used to assess muscle function.Results:In patients with myositis, mPGES-1, COX-2 and COX-1 expression was significantly higher compared to healthy individuals and associated with inflammatory cells. Double immunofluorescence demonstrated a predominant expression of mPGES-1 in macrophages. Conventional immunosuppressive treatment resulted in improved but still lower muscle function than normal. A decreased number of CD68-positive macrophages and reduced COX-2 expression in muscle tissue was also seen. By contrast, following the same treatment no significant changes were observed in muscle tissue regarding number of infiltrates, T lymphocytes, CD163-positive macrophages or mPGES-1 protein levels.Conclusions:Increased expression of mPGES-1, COX-1 and COX-2 at protein level was observed in muscle tissue from patients with myositis compared to healthy individuals. Conventional immunosuppressive treatment led to a significant downregulation of COX-2 in myositis muscle tissue. However, the expression of mPGES-1 and COX-1 remained unchanged indicating a role of these enzymes in the chronicity of these diseases.