Marked expression of IL-1 receptors in cell nuclei and muscle fiber membrane in muscle tissue of patients with idiopathic inflammatory myopathies

In chronic inflammatory diseases, IL-1 is known as an important proinflammatory cytokine inducing the expression of a variety of genes mediating the synthesis of several proteins, which can induce both acute and chronic inflammatory changes. Idiopathic inflammatory myopathies, such as polymyositis and dermatomyositis, are chronic autoimmune muscle disorders characterised by proximal muscle weakness and histopathological signs of patchy distribution of inflammatory cells in the skeletal muscle. Muscle tissue of patients with such myopathies has been shown to have an increased expression of IL-1α and IL-1β; however, the expression and pathophysiological role of IL-1 receptors in muscle tissue from such patients and healthy subjects has not yet been elucidated.

To investigate the expression of IL-1 receptors in muscle tissue from both patients and healthy subjects and to describe whether IL-1 receptors are differentially expressed in symptomatic and non-symptomatic muscle tissue of patients with polymyositis and dermatomyositis.

Muscle biopsies from eight patients with polymyositis, three patients with dermatomyositis, and six healthy subjects were included in this study. Muscle biopsies were taken from two different sites, one from a symptomatic muscle and another biopsy from a non-symptomatic muscle. IL-1α, IL-1RI, and IL-1RII expression were investigated by immunohistochemistry. IL-1RI and IL-1RII were also investigated by confocal microscopy.

In patients with polymyositis and dermatomyositis, IL-1α was found to be expressed in endothelial cells and inflammatory cells, and significantly increased in symptomatic when compared with non-symptomatic muscle tissue. IL-1α was not expressed in muscle tissue of healthy subjects. In patients, IL-1RI and IL-1RII were strongly expressed in inflammatory cells, endothelial cells, in the membrane of the muscle fiber, as well as in the nucleus of the muscle fiber of patients, whereas in muscle tissue of healthy subjects only a scattered pattern of IL-1RI and IL-1RII expression in a few endothelial cells and in a few of nuclei of the muscle fiber could be observed. The membrane and nuclear expression were confirmed by double stainings.

This is the first study to show the expression of IL-1RI and IL-1RII in the cell nuclei and in the membrane of muscle fibers. Moreover, we have found some marked differences between symptomatic and non-symptomatic muscle tissue of patients and healthy subjects indicating a potentially important role of IL-1 receptors in the pathogenesis of idiopathic inflammatory myopathies.

Affiliations

1. Department of Rheumatology, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden

   • C Grundtman
   • , S Salomonsson
   • , C Dorph
   •  & IE Lundberg

2. Department of Physiology, Karolinska Institutet, Stockholm, Sweden

   • J Burton

3. Department of Woman and Child Health, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden

   • U Andersson

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