Interleukin-8

Author: Prof. Dr. med. Peter Altmeyer

Last updated on: 01.10.2023

Synonym(s)

Anionic neutrophil activating peptides β2 (ANAP β2); Chemotactic monokine; Chemotactic skin-reactive activity; Chemotaxine; Dermal fibroblast derived cytokines; Endothelial cell neutrophil-activating peptides β (EDNAP β); Endothelial derived neutrophil activating peptides (EDNAP); Fibroblast derived neutrophil-activating peptide/protein (FDNAP); Granulocyte chemotactic factor (GCF); Granulocyte chemotactic peptide/protein (GCP); IL-8; LDNAP); Leukocyte adhesion inhibitor (LAI); Leukocyte derived neutrophil activating peptides (LDNAP); Leukocyte inhibitory factor (LIF); Lung carcinoma derived chemotaxin (LUCT); Lymphocytes chemotactic factors (LCF); Lymphocytes derived neutrophil-activating peptides (LYNAP; Lymphocytes derived neutrophil-activating peptides (LYNAP LDNAP); Monocyte derived chemotaxin (MOC); Monocyte derived neutrophil activating factor (MDNAF); Monocyte derived neutrophil activating peptides (MDNAP oder MONAP); Monocyte derived neutrophil chemotactic factor (MDNCF); neutrophil activating factor (NAF); Neutrophil-activating protein/peptides 1 (NAP-1); Neutrophilic chemotactic factor (NCF); Neutrophilic chemotactic peptide/protein (NCP); psoriatic leukotactic factor (PLF); T cell chemotactic factor (TCF); T-lymphocyte chemotactic factor (TCF); Tumor necrosis factor-stimulated gene sequences (TSG-1); Tumor necrosis factor-stimulated gene sequences (TSG-1).

Definition
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Interleukin-8 is a chemokine produced mainly by stimulated monocytes, but also by macrophages, endothelial cells, hepatocytes, keratinocytes, melanocytes, fibroblasts and various tumor cell lines. Interleukin-8 is encoded by a gene (interleukin-8 gene/alias CXCL8 gene = C-X-C Motif Chemokine Ligand 8), which in humans is located on chromosome 4, where it forms a gene cluster with other cytokine genes.

Its synthesis can be stimulated in many cell types by interleukin-1, interleukin-2, interleukin-3, GMC-SF (granulocyte-monocyte colony-stimulating factor), and TNFalpha. In addition, the formation of interleukin-8 is induced by viruses, bacterial lipopolysaccharides, phytohemagglutinins, and others.

Glucocorticoids such as dexamethasone and betamethasone inhibit production; so do interferon gamma, interleukin-4, and 5'-lipoxygenase inhibitors.

Interleukin-8 is chemotactic for neutrophils and T lymphocytes. IL-8 initiates epidermal proliferation.

Interleukin-8 serves as a mediator in a number of acute and chronic diseases. By activating neutrophil granulocytes, the cytokine is involved in inflammatory responses, especially in the initiation and maintenance of rheumatic diseases. Furthermore, it promotes angiogenesis via activation of vascular endothelial growth factor(VEGF) and matrix metalloproteinase-2, and thus also plays an important role in tumor growth and wound healing. Interleukin-8 is overexpressed in gastric mucosa infected by Helicobacter pylori. In psoriatic lesions, interleukin-8 is overexpressed.

Meta-analyses have confirmed that UVB irradiation in psoriasis lowers serum levels of VEGF and interleukin-8....

A "-251T/A polymorphism" in the promoter region of the interleukin-8 gene increases the risk of developing various carcinomas. A "-251T/A polymorphism" in the promoter region of the interleukin-8 gene increases the risk of various carcinomas, such as breast carcinoma, gastric carcinoma and nasopharyngeal carcinoma.

General information
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In detail, interleukin-8 specifically activates neutrophil granulocytes in which chemotaxis and adhesion readiness (expression of adhesion molecules) are increased. Furthermore, an activation of the so-called "oxidative burst" occurs. In basophilic granulocytes and mast cells Il-8 triggers the release of histamine and leukotriene. The cytokine has a chemotactic and activating effect on T-lymphocytes, but inhibits the production of immunoglobulin E (IgE).

Note(s)
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Interleukin-8 is a ligand for 2 membrane receptors(CD128 also known as CXCR1and CXR2). These are encoded by different genes both located on chromosome 2 (gene locus q33-q36).

These two types of receptors for interleukin-8 are expressed by numerous cell types: but they are largely identical in structure and functionality. Both also function as receptors for other cytokines such as "macrophage inflammatory protein 2 (MIP-2; MIP)", "melanoma growth stimulatory activity (MGSA)" or "neutrophil activating protein-2 (NAP-2)". Signal transduction proceeds independently of the stimulating ligand via a G protein, and leads to activation of adenyl cyclases, MAP kinases, and an intracellular increase in Ca2+ concentration.

Literature
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Chen HQ et al,(2016) Effects of Narrow Band Ultraviolet B on Serum Levels of Vascular Endothelial Growth Factor and Interleukin-8 in Patients with Psoriasis. On J Ther 23:e655-662.
Dong R et al (2015) Interleukin-8: A critical chemokine in biliary atresia. J Gastroenterol Hepatol 30:970-976.
Jin WJ et al (2014) Diagnostic value of interleukin-8 in colorectal cancer: a case-control study and meta-analysis. World J Gastroenterol 20:16334-16342.
Jundi K et al (2015) Transcription of Interleukin-8: How Altered Regulation Can Affect Cystic Fibrosis Lung Disease. Biomolecules 5:1386-1398.
Kotyza J (2012) Interleukin-8 (CXCL8) in tumor associated non-vascular extracellular fluids: its diagnostic and prognostic values. A review. Int J Biol Markers 27:169-178.
Lee KE et al (2013) Helicobacter pylori and interleukin-8 in gastric cancer. World J Gastroenterol 19:8192-8202.
Qin B et al. (2016) Interleukin-8 gene
polymorphismns -251T>A contributes to Alzheimer's disease susceptibility. Medicine (Baltimore) 95:e5039.
Wang N et al (2012) -251 T/A polymorphism of the interleukin-8 gene and cancer risk: a HuGE review and meta-analysis based on 42 case-control studies. Mol Biol Rep 39:2831-2841.
Zarogoulidis P et al (2014) Interleukin-8 and interleukin-17 for cancer. Cancer Invest 32:197-205.
Zhou M et al (2015) Interleukin-8 for diagnosis of neonatal sepsis: a meta-analysis. PLoS One 10:e0127170.