The Biology of Interleukin-6

来自 dx.doi.org

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阅读量：

238

作者：

T Kishimoto

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摘要：

Most cytokines involved in the regulation of the immune responses and hematopoiesis have been molecularly cloned. The studies with recombinant molecules clearly demonstrate that the function of these cytokines is not specific to a certain lineage of cells as originally expected but they show a wide variety of biological functions on various tissues and cells. One of the most typical examples of these multifunctional cytokines is IL-6. As described, it regulates immune responses, hematopoiesis, and acute phase reactions, indicating that it plays a central role in host defense mechanism. Among many cytokines, IL-6 is the first one, the abnormal expression of which is directly related to the pathogenesis of several diseases, such as myeloma/plasmacytoma, Castleman's disease, and mesangium proliferative glomerulonephritis, in which IL-6 functions as an autocrine growth factor for kidney mesangium cells. Therefore, the study on the regulatory mechanism of the IL-6 gene expression is indispensable for unraveling the molecular pathogenesis of those diseases. Neutralization of IL-6 with specific inhibitors may be applied for the treatment of such diseases. Soluble receptors are possible candidates as the specific inhibitor. The signal transduction through cytokine receptors may be unique: (a) the number of receptors is approximately 100-fold less than that of hormone or growth factor receptors and (b) any known biochemical reactions, such as phosphatidyl inositol turnover, tyrosine phosphorylation, and Ca++-ion influx, are not invoked following stimulation with cytokines. Recently, cDNAs for cytokine receptors, such as IL-6, IL-1 and γ-IFN have been cloned. The receptor molecules do not have any unique structure for the signal transduction, such as tyrosine kinase domain. Therefore, the presence of associated molecules for the signal transduction is assumed. In fact, IL-6 stimulation triggers the association of the IL-6 receptor with a nonligand binding signal transducer. The unique mechanism of signal transduction through cytokine receptors will hopefully be elucidated in the near future.

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关键词：

Animals Humans Plasmacytoma Autoimmune Diseases Acute-Phase Reaction Interleukin-6 Hematopoiesis

DOI：

10.1182/blood.V74.1.1.bloodjournal7411

被引量：

4411

年份：

1989