Increased IL-18 Production by Dendritic Cells in Active Inflammatory Myopathies
Inflammatory myopathies (IM) are chronic disorders characterized by muscular accumulation of inflammatory cells that promote cytotoxicity and tissue damage. Overexpression of chemokines and cytokines as well as imbalance of dendritic cells (DC) homeostasis have been postulated to exert a role in both dermatomyositis (DM) and polymyositis (PM). We studied the T helper (Th)-1 and Th2 cytokine levels by enzyme linked immunosorbent assay (ELISA) and the muscular expression of IL-18 and its receptor by both histochemistry (HIC) and in situ hybridization (ISH) in both patients and normal controls. Also, the cell populations infiltrating the muscles were investigated. We present evidence that DM and PM are characterized by a predominant Th1 immune response with high production of both interferon (IFN)-? and interleukin (IL)-18 in the presence of reduced levels of IL-4 and IL-6. IL-18 was also demonstrated in muscles and produced by both macrophages and DC surrounding either perivascular and perimysium areas or endomysium. IL-18R was highly expressed by T cells and DC as well as by endothelial cells (EC) and smooth muscle cells (SMC). High concentrations of serum and muscular IL-18 suggest that deregulated IL-18/IL-18R pathway may be pathogenetic in IM and measurement of IL-18 might be predictive of the disease activity
dendritic cells interleukin-18 myositis inflammation mcp-1