IL-8 (CXCL8)

IL-8 (interleukin-8, CXCL8) is a chemokine that recruits neutrophils to sites of infection and tissue damage, and doubles as a pro-angiogenic and pro-metastatic signal in tumors.

Function

IL-8 is secreted by macrophages and epithelial cells in response to inflammatory stimuli such as TNF and IL-1. It binds the G-protein-coupled receptors CXCR1 and CXCR2 on neutrophils, directing their migration along a gradient to the inflamed site, and also activates them for degranulation and respiratory burst. Its CXC chemokine motif with a glutamate-leucine-arginine sequence is what gives it both receptor specificity and angiogenic activity through CXCR2 on endothelial cells.

In cancer

Tumors produce IL-8 constitutively. The cytokine recruits neutrophils and myeloid-derived suppressor cells into the tumor, promotes angiogenesis, and acts directly on tumor cells through CXCR1/2 to drive epithelial–mesenchymal transition, stemness, and metastatic behavior. High IL-8 correlates with poor prognosis in melanoma, breast, and colorectal cancer, and with resistance to PD-1 blockade in some studies, which has made CXCR2 antagonists an active area of trial design.

Notes

• Human gene symbol: CXCL8; UniProt P10145; 99 amino acids (precursor); CXC chemokine family.
• The name “interleukin-8” predates the chemokine nomenclature; both names remain in use.