CXCL8

Chr 4

C-X-C motif chemokine ligand 8

Also known as: GCP-1, GCP1, IL8, LECT, LUCT, LYNAP, MDNCF, MONAP

The protein encoded by this gene is a member of the CXC chemokine family and is a major mediator of the inflammatory response. The encoded protein is commonly referred to as interleukin-8 (IL-8). IL-8 is secreted by mononuclear macrophages, neutrophils, eosinophils, T lymphocytes, epithelial cells, and fibroblasts. It functions as a chemotactic factor by guiding the neutrophils to the site of infection. Bacterial and viral products rapidly induce IL-8 expression. IL-8 also participates with other cytokines in the proinflammatory signaling cascade and plays a role in systemic inflammatory response syndrome (SIRS). This gene is believed to play a role in the pathogenesis of the lower respiratory tract infection bronchiolitis, a common respiratory tract disease caused by the respiratory syncytial virus (RSV). The overproduction of this proinflammatory protein is thought to cause the lung inflammation associated with csytic fibrosis. This proinflammatory protein is also suspected of playing a role in coronary artery disease and endothelial dysfunction. This protein is also secreted by tumor cells and promotes tumor migration, invasion, angiogenesis and metastasis. This chemokine is also a potent angiogenic factor. The binding of IL-8 to one of its receptors (IL-8RB/CXCR2) increases the permeability of blood vessels and increasing levels of IL-8 are positively correlated with increased severity of multiple disease outcomes (eg, sepsis). This gene and other members of the CXC chemokine gene family form a gene cluster in a region of chromosome 4q. [provided by RefSeq, May 2020]

GeneReviewsOMIMResearchGenerating clinical summary…
DNmechanismLOEUF 1.86
Clinical SummaryCXCL8
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
3 VUS of 13 total submissions
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
📖
GeneReview available — CXCL8
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.86LOEUF
pLI 0.000
Z-score -0.23
OE 1.12 (0.561.86)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-0.52Z-score
OE missense 1.21 (0.981.50)
59 obs / 48.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?1.12 (0.561.86)
00.351.4
Missense OE?1.21 (0.981.50)
00.61.4
Synonymous OE?1.14
01.21.6
LoF obs/exp: 5 / 4.5Missense obs/exp: 59 / 48.8Syn Z: -0.46

This gene — mechanism propensity

DN
0.78top 25%
GOF
0.4678th %ile
LOF
0.2387th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

13 submitted variants in ClinVar

Classification Summary

VUS3
Likely Benign3
3
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
3
0
0
3
Likely Benign
1
0
1
1
3
Benign
0
0
0
0
0
Total13116

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

24 pathogenic / likely-pathogenic (of 28) ClinVar copy-number / structural variants overlap CXCL8 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

CXCL8 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Breast Cancer Early Stage Breast Cancer (Stage 1-3)Prehabilitation

Multimodal Prehabilitation Program That Combines Physical Exercise, Psychological Intervention and Nutritional Support to Improve the Response to Neoadjuvant Chemoterhapy in Early Breast Cancer Patients

RECRUITING
NCT07107594Phase NAHospital Clinic of BarcelonaStarted 2025-01-14
Multimodal prehabilitation
PreDiabetesDysbiosisEndotoxemia

Assessing Gut Microbiota Mediated Health Outcomes of Whole Wheat and Its Major Bioactive Components

ACTIVE NOT RECRUITING
NCT05318183Phase NAOhio State UniversityStarted 2022-01-27
Whole Wheat BreadWhite Bread (control)
Porphyria, Acute Intermittent

Clinical Research on Acute Intermittent Porphyria and the Use of Carbohydrate-Rich Diet as a Treatment

RECRUITING
NCT06273644Phase NANordlandssykehuset HFStarted 2024-01-27
Carbohydrates
Adequate Vitamin C StatusInadequate Vitamin C Status

Anti-inflammatory Activities of Vitamin C Supplementation on the Gut Barrier Function in Adults With Obesity

RECRUITING
NCT07151105Phase NAOhio State UniversityStarted 2025-10-01
Vitamin C Supplement + Low Vitamin C DietPlacebo + Low Vitamin C Diet
Urinary Tract Infections

DIagnoSing Care hOme UTI Study

RECRUITING
NCT05880329University of SouthamptonStarted 2023-09-01
Candidate POCTs for detecting UTI
Concussion, BrainMild Traumatic Brain Injury

Risk Stratification in Children With Concussion

RECRUITING
NCT05825027Duke UniversityStarted 2023-05-23
Breast CancerCentral Nervous System Metastases

Predictive Factors for CNS Metastases in Early Breast Cancer Using Liquid Biopsy (AKRA CŽS)

ACTIVE NOT RECRUITING
NCT07447544Phase NAInstitute of Oncology LjubljanaStarted 2025-07-07
Primary Tumor mRNA Expression Profiling (NGS)Serum Chemokine Quantification (ELISA)
Cystic Fibrosis-related DiabetesCystic Fibrosis

Metformin for People With CFRD on CFTR Modulator Therapy to Improve Ion Channel Function

RECRUITING
NCT04530383Phase PHASE2University of Kansas Medical CenterStarted 2022-02-14
Metformin Hydrochloride
Hip OsteoarthritisArthroplasty, Replacement, HipPostoperative Complications

Preoperative Fasting and the Gut Microbiome Before Hip Replacement

RECRUITING
NCT07651462Phase NACharite University, Berlin, GermanyStarted 2025-07-01
Buchinger Fastenbox + intermittent fasting (20-day preoperative schedule)
Aging

Evaluation of the Efficacy of Calcium a -Ketoglutarate(AKG-Ca) in Improving Human Aging

ACTIVE NOT RECRUITING
NCT07114536Phase NAShenzhen Hygieia Biotech Co., LtdStarted 2025-08-20
Calcium-a-ketoglutaratePlacebo(starch)
Unrecognized Condition

Evaluate DF-003 in ex Vivo Assays Using Peripheral Blood Mononuclear Cell From Subjects With ROSAH Syndrome

RECRUITING
NCT05319132Hospices Civils de LyonStarted 2022-09-06
Adult subjects with ROSAH syndrome
Heart FailureDilated Cardiomyopathy

Myocardial Telomere Recapping Study for Dilated Cardiomyopathy

ACTIVE NOT RECRUITING
NCT05837143Phase EARLY_PHASE1Shanghai East HospitalStarted 2023-03-30
JV001