[Diseases associated with cytokine dysregulation].
Communication between cells is essential for a wide variety of biological functions. One way cells interact in immune and hemopoietic systems is through soluble mediators called interleukins or cytokines. Many cytokines and their receptors have been identified and characterized at the molecular level. These studies have observed that most cytokines function in a pleiotropic and redundant manner. Receptor studies have shown that many cytokine receptors consist of two polypeptide chains, a ligand-binding receptor, and a nonbinding signal transducer. This arrangement may explain the pleiotropic and redundant effects of cytokines. For example, leukemia inhibitory factor (LIF) and IL-6 share many biological activities including platelet production, and the receptors of these cytokines utilize gp130 as a common signal transducer. IL-6 is multifunctional and produces both favorable and unfavorable effects on human health. Dysregulation of IL-6 expression is linked to the occurrence of cancer and autoimmune diseases, such as multiple myeloma, Castleman's disease, mesangial proliferative glomerulonephritis, and rheumatoid arthritis. Studies in transgenic mice in which the IL-6 gene was overexpressed have confirmed these pathogenic actions of IL-6. The pathogenesis of these diseases and therapies to treat them are discussed here based on insights derived from cytokine research.
Kishimoto
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Department of Internal Medicine III, Osaka University Medical School.
D000818:Animals; D000917:Antibody Formation; D001327:Autoimmune Diseases / Q000209:etiology / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002097:C-Reactive Protein / Q000096:biosynthesis; D002454:Cell Differentiation; D002455:Cell Division; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D009369:Neoplasms / Q000209:etiology / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D019947:Receptors, Interleukin-6; D013601:T-Lymphocytes / Q000276:immunology*
D015850:Interleukin-6; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6; D002097:C-Reactive Protein