Interleukin-6

Interleukin-6 is a proinflammatory glycoprotein consisting of 184 amino acids. In humans, the gene encoding interleukin-6 is located on the 7th chromosome.

Interleukin-6 binds to specific interleukin-6 receptors(IL-6R = CD126) and forms complexes with them that 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 as well as on B-cell lymphoma cells. 200-1500 receptors are expressed per cell.The gene encoding interleukin-6 is located on the 7th chromosome.

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

The cytokine is significantly involved in the regulation of humoral and cell-mediated immune defense. It promotes the differentiation of CD4+ lymphocytes into Th17 cells. The cytokine further causes the differentiation of B lymphocytes and macrophages and the maturation of megakaryocytes and osteoclasts. The cytokine stimulates the synthesis of immunoglobulins G and M, the "oxidative burst" in monocytes and neutrophil 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 together with interleukin-1 and TNFalpha acts as an endogenous pyrogen.

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

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

Still experimental are therapy studies with monoclonal antibodies blocking the IL-6 receptor(tocilizumab) in systemic amyloidosis.

A smaller study with tocilizumab exists for systemic lupus erythematosus. Significant improvement was seen in disease activity of SLE in 8 of 15 pat. Arthritis improved in 7 pat. DNA-AK levels decreased, as did IgG levels.
Single case reports are available of positive effects in systemic scleroderma.

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.

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.