Therapeutic strategies for SLE involving cytokines: mechanism-oriented therapies especially IFN-gamma targeting gene therapy.
Systemic lupus erythematosus (SLE: lupus) is a chronic complicated autoimmune disease and pathogenesis is still unclear. However, key cytokines have been recognized. Interferon (IFN)-γ and also IFNalpha/beta are of particular importance. Depending on the concept that lupus is a helper T(Th)1 disease and that dendritic cells (DCs) determine the direction of lupus, balance shift of Th1/Th2 and immunogenic/tolerogenic DCs is reviewed for therapy. (IFN)-gamma- and IFN-alpha/beta-targeted (gene) therapies are introduced. These consist of Th1/Th2 balance shift and elimination of IFN-gamma and IFN-gamma-related cytokines such as (interleukin)IL-12 and IL-18. Other approaches include suppression of immunocompetent cells, normalization of abnormal T-cell function, costimulation blockade, B lymphocyte stimulator (Blys) blockade, and suppression of nephritic kidney inflammation. Moreover, balance shift of IFN-alpha/beta and tumor necrosis factor (TNF)-alpha together with regulatory T(Treg) cells are briefly introduced. Clinical application will be discussed.
Hayashi
Toshiharu
T
Laboratory of Veterinary Pathology, Faculty of Agriculture, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, Japan. hayasi@yamaguchi-u.ac.jp
D000818:Animals; D016207:Cytokines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D015316:Genetic Therapy; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics* / Q000627:therapeutic use*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000628:therapy*; D018417:Th1 Cells / Q000276:immunology
D016207:Cytokines; D007371:Interferon-gamma
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