Interleukin-6

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 19.10.2021

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Synonym(s)

26 kDa protein; B cell stimulation factor 2 (BSF-2); B cell stimulation factor p2 (BSF-p2); B cell stimulatory factor 2 (BSF-2); B cell stimulatory factor (BCSF); CDF); Choline acetyltransferase development factor (CAT development factor; Choline acetyltransferase development factor (CAT development factor CDF); Colony promoting activity (CPA); Cytolytic differentiation factor for T lymphocytes (CDF); Cytotoxic T cell differentiation factor; differentiation inducing factor (DIF); Differentiation inducing factor for human monoblastic leukemia cells; Fibroblast derived differentiation inducing factor for human monoblastic leukemia cells; fibroblast-derived growth inhibitor (FDGI); Haematopoietic CSF 309; hepatocyte stimulating factor (HSF); Hepatocyte stimulatory factor 1 (HSF-1); Hepatocyte stimulatory factor (HSF); HP1; Human endothelial culture supernatant (HECS); hybridoma growth factor (HGF); Hybridoma growth factor (HGF); hybridoma/plasmacytoma growth factor (HPGF); Hybridoma/plasmacytoma growth factor (HPGF); IL-6; Interferon β2 (INF-β2); Interleukin 6IL-6B cell differentiation factor (BCDF); interleukin-haemopoietin-1 (Il-HP1); interleukin hybridoma/plasmacytoma-1 (ILHP1); Interleukin hybridoma/plasmacytoma-1 (ILHP1); macrophage-granulocyte inducer 2 (MGI-2); Macrophage-granulocyte inducing protein 2A (MGI-2A); Monocyte derived human B cell growth factor; Murine lung-derived growth inhibitory factor (L-GI factor); myeloma growth factor; natural killer cell activating factor (NKAF); plasmacytoma growth factor (PCT-GF oder PGF); T cell activating factor (TAF); Thymocyte growth factor (THCGF); Thymocyte stimulating factor (TSF); WI-26-VA4 factor; WI-26-VA4 factor.

Definition
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Interleukin-6 is a pro-inflammatory glycoprotein consisting of 184 amino acids. The gene coding for interleukin-6 is located on the 7th chromosome in humans.

Interleukin-6 binds to specific interleukin-6 receptors (IL-6R = CD126) and forms complexes with them, which bind to the ubiquitous membrane-bound gp-130. The receptors for interleukin-6 are located on T lymphocytes, on activated B lymphocytes, on monocytes, hepatocytes and on B-cell lymphoma cells. 200-1500 receptors are expressed per cell and the gene coding for interleukin-6 is located on the 7th chromosome.

Interleukin-6 is mainly secreted by monocytes/macrophages, but also by epithelial and endothelial cells. Interleukin-6 has broad biological effects.

The cytokine is essentially involved in the regulation of the humoral and cell-mediated immune defence. It promotes the differentiation of CD4+ lymphocytes into Th17 cells. The cytokine also causes the differentiation of B-lymphocytes and macrophages as well as the maturation of megakaryocytes and osteoclasts. The cytokine stimulates the synthesis of the immunoglobulins G and M, the "oxidative burst" in monocytes and neutrophilic granulocytes. Interleukin-6 induces the secretion of acute phase proteins in the liver (C-reactive protein, ferritin, serum amyloid A) as well as the production of other cytokines and acts together with interleukin-1 and TNFalpha as an endogenous pyrogen.

Interleukin-6 stimulates the release of ACTH from the pituitary gland; the resulting glucocorticoids in turn inhibit the production of interleukin-6 (negative feedback between the immune system and the neuroendocrine system).

General information
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Standard value: The standard value is up to 10 µg/ml

General therapy
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Still experimental are therapy physicians with monoclonal antibodies that block the IL-6 receptor(tocilizumab) in systemic amlyoidosis.

A smaller study with tocilizumab exists for systemic lupus erythematosus. A significant improvement in the disease activity of SLE was found in 8 out of 15 patients. Arthritis improved in 7 patients, and the concentration of DNA-AK was reduced, as were IgG levels.
There are single case reports of positive effects in systemic scleroderma.

Note(s)
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Overexpression of interleukin-6 results in a strong increase in serum IgG1 concentration with possible development of glomerulonephritis. In addition, an increased serum concentration of interleukin-6 appears to be involved in the development of a variety of diseases, e.g. chronic polyarthritis, myeloma, lymphomas, rheumatoid arthritis and liver cirrhosis.

Polymorphisms in the interleukin-6 gene (IL-6-174G/C and IL-6-572G/C) appear to increase the risk of systemic lupus erythematosus.

Literature
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  1. Cui YX et al (2015) Association of the interleukin-6 polymorphisms with systemic lupus erythematosus: a meta-analysis. Lupus 24:1308-1317.
  2. Frech TM et al (2015) Protective role of interleukin-6 in systemic sclerosis gastrointestinal tract involvement: case report and review of the literature. Clin Exp Rheumatol 33(4 Suppl 91):S179-181.
  3. Hartman J et al (2014) Inflammation and atherosclerosis: a review of the role of interleukin-6 in the development of atherosclerosis and the potential for targeted drug therapy. Cardiol Rev 22:147-151.
  4. Hou H et al (2015) Association of interleukin-6 gene polymorphism with coronary artery disease: an updated systematic review and cumulative meta-analysis. Inflamm Res 64:707-720.
  5. Kawahara Y et al (2014) Persistent fever and weight loss due to an interleukin-6-producing adrenocortical oncocytoma in a girl-review of the literature. Eur J Pediatr 173:1107-1110.
  6. Kumari N et al (2016) Role of interleukin-6 in cancer progression and therapeutic resistance. Tumour Biol 37:11553-11572.
  7. Lane T et al (2015) Therapeutic blockade of interleukin-6 by tocilizumab in the management of AA amyloidosis and chronic inflammatory disorders: a case series and review of the literature. Clin Exp Rheumatol 33(6 Suppl 94):S46-53.
  8. Liu X et al (2016) The biology behind interleukin-6 targeted interventions. Curr Opin Rheumatol 28:152-160.

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Last updated on: 19.10.2021