Interleukin-18 overexpression as a hallmark of the activity of autoimmune inflammatory myopathies.
The objective of this study was to explore the role of interleukin (IL)-18 in patients with inflammatory myopathies (IM) such as dermatomyositis (DM) and polymyositis (PM) in relation to the possible predominance of a Th1 immune response in their pathogenesis. Serum concentrations of IL-18, interferon (IFN)-gamma, IL-4 and IL-6 were measured in six patients by enzyme-linked immunosorbent assay (ELISA). IL-18 expression was evaluated by in situ hybridization (ISH), whereas CD68, CD8 and CD83 were investigated by immunohistochemistry (IHC) to define the main producers of IL-18. Lastly, the expression of both IL-18 receptor (IL-18R) and monocyte chemoattractant protein (MCP)-1 was also explored by IHC. High serum levels of IL-18 and IFN-gamma, and conversely low titres of IL-4 and IL-6, were demonstrated in both diseases. In addition, IL-18 was overexpressed in muscle biopsy specimens from patients with IM. Both macrophages and dendritic cells (DC) surrounding either perivascular and perimysium areas in DM or endomysium in PM were the main producers of IL-18. Endothelial cells (EC), smooth muscle cells (SMC) and CD8(+) T cells expressed a high content of IL-18R. Vessel cells overexpressed MCP-1 in parallel with IL-18R. High concentrations of serum IL-18 as well as muscular up-regulation of IL-18 and IL-18R suggest that deregulation of the IL-18/IL-18R pathway is a pathogenetic mechanism in IM. Measurement of IL-18 may thus predict the severity of both DM and PM.
Tucci
M
M
DIMO, Department of Internal Medicine and Clinical Oncology, University of Bari, Italy.
Quatraro
C
C
Dammacco
F
F
Silvestris
F
F
D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018932:Chemokine CCL2 / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D003882:Dermatomyositis / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D020382:Interleukin-18 / Q000097:blood / Q000378:metabolism*; D015847:Interleukin-4 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008264:Macrophages / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000276:immunology; D009220:Myositis / Q000276:immunology*; D017285:Polymyositis / Q000276:immunology; D053724:Receptors, Interleukin-18 / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D020382:Interleukin-18; D015850:Interleukin-6; D053724:Receptors, Interleukin-18; D015847:Interleukin-4; D007371:Interferon-gamma