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تسجيل

The Major Proinflammatory Cytokines of Innate Immunity: Interleukin-6

المؤلف:  Abbas, A. K., Lichtman, A. H., Pillai, S., & Henrickson, S. E.

المصدر:  Cellular and Molecular Immunology (2026)

الجزء والصفحة:  11E, P93

2026-05-05

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IL-6 is another important cytokine in acute inflammatory responses that has both local and systemic effects. It induces the synthesis of acute-phase reactants by the liver and promotes the differentiation of IL-17–producing helper T cells. IL-6 is synthesized by mononuclear phagocytes, DCs, vascular endothelial cells, fibroblasts, and other cells in response to PAMPs and DAMPs and in response to IL-1 and TNF. IL-6 is a homodimer that belongs to the type I cytokine family. The receptor for IL-6 consists of a cytokine-binding polypeptide chain and a signal-transducing subunit (called gp130) that is also the signaling component of receptors for other cytokines. The gp130 subunit is expressed on many cell types, but the IL-6 binding chain is expressed only by leukocytes and hepatocytes, as a transmembrane protein in association with gp130. A soluble form of the IL-6 binding chain is generated by proteolytic cleavage of the membrane form and is present in blood and tissue fluids. This soluble form can bind IL-6, and then the complex can associate with the extracellular part of gp130 on many cell types and initiate signaling. This mechanism is called trans-signaling. The IL-6 receptor engages a signaling pathway that activates the transcription factor STAT3. IL-6 is a major contributor to inflammation in several human inflammatory diseases, including rheumatoid arthritis, and antibodies specific for the IL-6 receptor are used to treat some forms of arthritis. Some lymphoproliferative disorders, such as Castleman disease, are caused by human herpesvirus–8 (HHV 8), a virus that encodes a homolog of IL-6, and IL-6 blockade has been used to treat these diseases.