Table 2 Role of the CXCL8-CXCR1/CXCR2 axis in diseases

Cancer

Promoting tumor survival, growth & migration

Stimulating neovascularization in the tumor

Inducing epithelial-to-mesenchymal transition, promoting invasion & metastasis

Recruiting tumor-associated neutrophils (anti-tumor N1 & pro-tumor N2)

Recruiting CXCR1- or CXCR2-expressing MDSCs

Stimulating NETs release, which can coat tumor cells shielding them from immune cytotoxicity

Recruiting tumor-associated macrophages & inducing an immunosuppressive M2 phenotype

Promoting recruitment & proliferation of CXCR1/CXCR2-expressing cancer stem cells

Inducing resistance to anti-tumor therapy

Some rare studies indicate an anti-tumor effect of CXCL8

[57]

[57]

[104, 105]

[107]

[108, 109]

[110]

[111]

[71, 105]

[112, 113]

[118, 119]

Cardiovascular diseases

Atherosclerosis

Inducing adhesion and chemotaxis of CXCR2-expressing foam cells & neutrophils

Contributing to the early phase of atherosclerotic plaque formation

Recruiting bone marrow endothelial progenitor cells promoting atherosclerotic plaque resolution

[21]

[21]

[120]

Myocardial infarction

Promoting angiogenesis, neutrophil infiltration & infarction size

[121]

Arterial hypertension

Promoting hypertension & vascular dysfunction by recruiting CXCR2⁺ pro-inflammatory cells

[122]

Pulmonary diseases

Acute lung injury/ARDS

Recruiting neutrophils, leading to neutrophil-associated damage

Immune complexes of anti-CXCL8 autoantibodies suppress spontaneous neutrophil apoptosis

[21, 124]

[123]

Cystic fibrosis

Recruiting neutrophils

CXCR1 expression on neutrophils is important for clearance of bacterial infections

Promoting airway hyperresponsiveness by inducing contraction of airway smooth muscle cells

[125]

[21, 126]

[21]

Asthma

Recruiting neutrophils

Inducing bronchoconstriction by stimulating CXCR1/CXCR2-expressing airway smooth muscle cells

Promoting angiogenesis of peribronchial blood vessels during allergic airway remodeling

[21]

[21]

[21]

COPD

Recruiting neutrophils and CXCR2-expressing macrophages

Neutrophilic proteases destroy tissue of the small airways

[125, 127]

[128,129,130]

IPF

Recruiting neutrophils

Promoting angiogenesis

Promoting collagen deposition & fibrosis

[133]

[134, 135]

[134]

Transplantation & IRI

Transplantation

Recruiting neutrophils leading to neutrophil-associated damage

Rejection of transplanted organs

[136, 137]

[136, 137]

IRI

Recruiting neutrophils leading to neutrophil-associated damage

[138,139,140]

Arthritic diseases & pain

Arthritic diseases

Recruiting & activating neutrophils

Promoting angiogenesis

Maintaining chondrocyte phenotypic stability in chronic osteoarthritis

[142,143,144]

[147]

[153]

Pain

Inducing sympathetic & neuropathic pain

[150,151,152]

Neurological diseases

Multiple sclerosis

Recruiting neutrophils

Inducing blood-brain-barrier breakdown & development of autoimmune demyelination

Uncertain effects on remyelination

[154, 156]

[154, 156]

[21, 154, 157]

Alzheimer’s disease

Protecting human neurons from amyloid-β-induced neurotoxicity

Inducing microgliosis and oxidative stress

[158]

[159]

Kidney diseases & diabetes

Kidney diseases

Recruiting neutrophils & mediating damage to the kidneys

[21]

Diabetes

Inducing pathogenesis of type 1 diabetes & diabetic kidney disease in type 2 diabetes

[160, 161]

Auto-immune diseases

Psoriasis

Autocrine stimulation of CXCR2-expressing keratinocytes in skin lesions

Recruiting neutrophils

Stimulating angiogenesis

[21]

[21]

[21]

SLE

High levels & a CXCL8 single nucleotide polymorphism are associated with severe disease

[80, 163]

Inflammatory bowel diseases

Recruiting & activating neutrophils and macrophages for clearance of pathogens

Neutrophil-associated inflammatory damage

Crosstalk between innate and adaptive immunity

[21]

[21]

[165]

Infectious diseases

General

Recruiting & activating neutrophils for clearance of pathogens

Neutrophil-associated inflammatory damage

[21]

[21]

COVID-19

Increased activation state of circulating blood neutrophils

Hyperactivated neutrophils in the lungs with severe proteolytic activity

Pro-thrombotic neutrophils, characterized by degranulation and NET formation

Anti-CXCL8 autoantibodies may reduce the severe systemic inflammation

[166]

[168]

[169]

[170]

Sepsis

Recruiting neutrophils & releasing NETs inducing bacterial clearance & tissue damage

CXCR2 desensitization impairs adequate control of microbial dissemination

Phospholipase D2 (PLD2) downregulates CXCR2 and inhibits NET release driving mortality

[21, 171]

[21]

[172]