IL8
Interleukin 8
Gene Number: 3576
Location: 4q13.3
Key Functions: Chemotaxis, inflammation, neutrophil recruitment, immune signaling
The IL8 gene encodes interleukin-8 (CXCL8), a small yet powerful signaling molecule at the crossroads of inflammation and immunity. Functionally, IL-8 belongs to the CXC chemokine family, acting as a messenger that guides neutrophils — the immune system’s rapid-response soldiers — to sites of infection, tissue damage, or stress.
When the body detects danger, such as invading microbes or cellular injury, immune and epithelial cells release IL-8 in response to pro-inflammatory cytokines like IL-1β and TNF-α. Once secreted, IL-8 binds to its receptors, CXCR1 and CXCR2, on the surface of neutrophils. This receptor engagement triggers directed movement (chemotaxis), causing neutrophils to migrate toward the source of inflammation, where they unleash reactive oxygen species, antimicrobial peptides, and enzymes to neutralize pathogens and clear debris.
On a molecular level, IL-8 signaling operates through G protein–coupled receptor (GPCR) pathways. Binding to CXCR1/2 activates intracellular cascades involving phospholipase C (PLC), MAPK, and PI3K/AKT, promoting not only migration but also cell survival and degranulation. Through these tightly coordinated mechanisms, IL-8 orchestrates the acute inflammatory response necessary for tissue defense and repair.
From a genetic standpoint, variation in the IL8 gene can significantly affect inflammatory tone and disease susceptibility. Polymorphisms in its promoter region — notably rs4073 (-251A/T) and rs2227306 (C/T) — have been linked to altered IL-8 expression. The -251A allele, for example, is associated with higher transcriptional activity, leading to increased IL-8 secretion. This hyperinflammatory genotype correlates with greater risk for chronic obstructive pulmonary disease (COPD), gastric cancer, rheumatoid arthritis, and inflammatory bowel disease.
Elevated IL-8 is not only a marker of inflammation but also a driver of pathology when regulation fails. In cancer biology, tumors often hijack IL-8 signaling to their advantage. The cytokine promotes angiogenesis, enhances tumor cell migration, and recruits immunosuppressive myeloid cells into the tumor microenvironment, facilitating metastasis and immune evasion. Consequently, IL-8 and its receptors are under active investigation as therapeutic targets in oncology and chronic inflammatory disorders.
In summary, IL8 exemplifies the dual nature of inflammation — essential for defense, yet destructive when unchecked. Its genetic and molecular dynamics reveal how a single chemokine can pivot between healing and harm, linking innate immune precision to the complex web of chronic disease and tissue homeostasis.
SNP ID | Your Genotype | Alternative Alleles | Interpretation |
|---|---|---|---|
rs4073 | No matching variant or no valid DNA data | T | No interpretation available |
rs2227306 | No matching variant or no valid DNA data | T | No interpretation available |
rs4073
AA – Lower IL-8 expression; typically associated with reduced inflammation risk and better outcomes in several conditions, including lymphoid cancers and sepsis (R).
AT – Intermediate IL-8 expression; A may confer partial protection (R).
TT – Increases IL-8 expression in response to LPS and is associated with elevated inflammatory responses (R).
Functional effect: The T allele upregulates IL-8 transcription under inflammatory stimuli, increasing inflammatory cytokine levels and auto-immunity.
rs2227306
CC – Associated with increased IL-8 transcription and elevated cytokine release; variant linked to higher risk of graves disease (R, R).
CT – Likely intermediate effect on IL-8 expression and inflammation markers (R).
TT – Associated with normal IL-8 levels; may reduce inflammation risk (R).
Functional effect: The C allele increases IL-8 transcription and is linked to higher inflammation, particularly in asthma and bronchial conditions (R).
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