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GeneE
50 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CXCL8
C-X-C motif chemokine ligand 8
Chromosome 4 · 4q13.3
NCBI Gene: 3576Ensembl: ENSG00000169429.13HGNC: HGNC:6025UniProt: C9J4T6
2,501PubMed Papers
20Diseases
2Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
Clinical Trials
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
response to molecule of bacterial originpositive regulation of angiogenesisembryonic digestive tract developmentnegative regulation of cell adhesion molecule productioncoronary artery diseaseIschemic strokemyocardial infarctionendocrine system disease
✦AI Summary

CXCL8 (interleukin-8) is the most potent human neutrophil-attracting chemokine 1 that mediates inflammatory responses by recruiting neutrophils, basophils, and T cells through binding to G-protein-coupled receptors CXCR1 and CXCR2 1. Upon receptor activation, CXCL8 triggers PI3K and MAPK signaling cascades, facilitating both leukocyte chemotaxis and activation 1. Beyond acute inflammation, CXCL8 plays critical roles in disease pathogenesis. In psoriasis, IL-17A upregulates CXCL8 production in keratinocytes, driving neutrophil recruitment and perpetuating epidermal inflammation 2. In gastric cancer, tumor-associated macrophage-derived CXCL8 suppresses CD8+ T cell infiltration and induces PD-L1 expression on macrophages, promoting immune evasion 3. Similarly, in glioblastoma, hypoxia-induced CXCL8 secretion recruits immunosuppressive macrophages via ALKBH5-mediated epitranscriptomic regulation 4. Clinically, elevated CXCL8 correlates with poor prognosis in multiple cancers, and CXCR2 inhibitors like reparixin demonstrate therapeutic potential in reversing immunosuppression 35. Additionally, respiratory viruses exploit the CXCL8/MAPK/hnRNP-K axis to enhance replication 6, while radiotherapy-induced CXCL8 mobilizes cytotoxic NK cells, linking senescence to antitumor immunity 7.

Sources cited
1
CXCL8 is the most potent human neutrophil-attracting chemokine; mediates interaction with CXCR1/CXCR2 and activates downstream signaling
PMID: 36725964
2
IL-17A upregulates CXCL8 production in keratinocytes to recruit neutrophils in psoriasis pathogenesis
PMID: 32070069
3
Tumor-associated macrophage-derived CXCL8 suppresses CD8+ T cell infiltration and induces PD-L1 expression, promoting immune evasion in gastric cancer
PMID: 30661053
4
Hypoxia-induced CXCL8 secretion via ALKBH5-mediated regulation recruits immunosuppressive tumor-associated macrophages in glioblastoma
PMID: 34670781
5
CXCL8 signaling blockade with reparixin sensitizes HNSCC to nutrient-starvation therapy by reducing tumor-associated macrophage-derived protective factors
PMID: 39905539
6
Respiratory viruses exploit the CXCL8/MAPK/hnRNP-K signaling axis to enhance viral replication
PMID: 39962077
7
Radiotherapy-induced CXCL8 secretion from senescent tumor cells recruits cytotoxic CD56dim NK cells to improve tumor control
PMID: 35319989
Disease Associationsⓘ20
coronary artery diseaseOpen Targets
0.35Weak
Ischemic strokeOpen Targets
0.34Weak
myocardial infarctionOpen Targets
0.34Weak
endocrine system diseaseOpen Targets
0.22Weak
placenta praeviaOpen Targets
0.21Weak
contact dermatitisOpen Targets
0.15Weak
melanomaOpen Targets
0.13Weak
neoplasmOpen Targets
0.13Weak
asthmaOpen Targets
0.13Weak
cancerOpen Targets
0.13Weak
oral squamous cell carcinomaOpen Targets
0.12Weak
hepatocellular carcinomaOpen Targets
0.12Weak
COVID-19Open Targets
0.12Weak
colorectal carcinomaOpen Targets
0.12Weak
cholangiocarcinomaOpen Targets
0.12Weak
gastric cancerOpen Targets
0.12Weak
ovarian cancerOpen Targets
0.12Weak
SepsisOpen Targets
0.12Weak
breast cancerOpen Targets
0.11Weak
triple-negative breast cancerOpen Targets
0.11Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets2
ABX-IL8Phase II
Interleukin-8 inhibitor
melanoma
ADAKITUGPhase II
Interleukin-8 inhibitor
Related Genes
ACKR1Protein interaction100%IL1RNProtein interaction100%CCL8Protein interaction100%CCR2Protein interaction100%CCL3L1Protein interaction100%CCL13Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
1%
Liver
0%
Brain
0%
Ovary
0%
Heart
0%
Gene Interaction Network
Click a node to explore
CXCL8ACKR1IL1RNCCL8CCR2CCL3L1CCL13
PROTEIN STRUCTURE
Preparing viewer…
PDB4XDX · 0.95 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.82LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.07 [0.57–1.82]
RankingsWhere CXCL8 stands among ~20K protein-coding genes
  • #34of 20,598
    Most Researched2,501 · top 1%
  • #16,673of 17,882
    Most Constrained (LOEUF)1.82
Genes detectedCXCL8
Sources retrieved50 papers
Response time—
📄 Sources
50▼
1
The chemokines CXCL8 and CXCL12: molecular and functional properties, role in disease and efforts towards pharmacological intervention.
PMID: 36725964
Cell Mol Immunol · 2023
1.00
2
Tumour-associated macrophages-derived CXCL8 determines immune evasion through autonomous PD-L1 expression in gastric cancer.
PMID: 30661053
Gut · 2019
0.90
3
SKAP1 Expression in Cancer Cells Enhances Colon Tumor Growth and Impairs Cytotoxic Immunity by Promoting Neutrophil Extracellular Trap Formation via the NFATc1/CXCL8 Axis.
PMID: 39269257
Adv Sci (Weinh) · 2024
0.88
4
CXCL8 secreted by immature granulocytes inhibits WT hematopoiesis in chronic myelomonocytic leukemia.
PMID: 39545419
J Clin Invest · 2024
0.86
5
Immunomarker profiling in human chronic wound swabs reveals IL-1 beta/IL-1RA and CXCL8/CXCL10 ratios as potential biomarkers for wound healing, infection status and regenerative stage.
PMID: 40200385
J Transl Med · 2025
0.80