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Expression of IL-18 in muscle tissue of patients with treatment-resistant idiopathic inflammatory myopathies

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Background

Idiopathic inflammatory myopathies, myositis, are characterized by infiltrates of T lymphocytes and macrophages in muscle tissue. Some patients with myositis are very resistant to immunosuppressive treatment. Thus new therapies are urgently required. An increased knowledge of the key molecular mechanisms in myositis would be important for development of new targeted therapies for these patients. IL-18 is a pleiotropic cytokine with proinflammatory and immunoregulatory effects. It has been shown to play an important pathogenic role in various autoimmune disorders (e.g. rheumatoid arthritis and Sjögrens syndrome). Whether IL-18 has a role in disease mechanism in myositis is not known.

Objective

To study the expression of IL-18 in muscle tissue of patients with idiopathic inflammatory myopathies.

Methods

Thirteen treatment-resistant patients, six polymyositis, four dermatomyositis, one juveline dermatomyositis, and two inclusion body myositis with signs of active muscle inflammation, were included in our study. Muscle biopsies were investigated by immunhistochemistry using monoclonal antibodies against IL-18.

Results

Intracellular IL-18 expression was detected in all patients with polymyositis, dermatomyositis and inclusion body myositis. The IL-18 expression was predominantly localized to inflammatory cells, in large infiltrates and scattered in tissue, in endothelial cells of capillaries (11/13), in fibroblast-like cells and smooth muscle cells.

Conclusion

This is the first study to demonstrate IL-18 expression at the protein level in muscle tissue from patients with idiopathic inflammatory myopathies. This was a consistent finding in mononuclear inflammatory cells in all three subsets of patients with treatment-resistant disease. These results suggest that IL-18 could have a role in the immunopathogenesis of myositis.

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Keywords

  • Rheumatoid Arthritis
  • Muscle Tissue
  • Myositis
  • Dermatomyositis
  • Inclusion Body Myositis