IL8

Interleukin-8 (IL-8), also known as CXCL8, is a chemokine of the CXC family produced by various cells, including macrophages, epithelial cells, and fibroblasts, in response to inflammatory stimuli. It plays a central role in innate immunity by directing the movement of neutrophils to sites of infection or damage and by activating neutrophil functions.

IL-8 serves as a potent chemoattractant for neutrophils, guiding them to inflammation sites and promoting degranulation and the respiratory burst. It can also affect endothelial cells and promote angiogenesis in certain contexts, contributing to tissue remodeling and, in some cancers, tumor progression and metastasis through actions on surrounding vasculature.

The activity of IL-8 is mediated primarily through two receptors, CXCR1 and CXCR2, which are expressed on neutrophils and other cell types. In humans, the IL8 gene is located on chromosome 4 and encodes a 99-amino-acid precursor that is processed into the active ~72-amino-acid chemokine. IL-8 expression is upregulated by pro-inflammatory signals such as IL-1 and TNF and is regulated in part by NF-κB.

Species differences are notable: in mice and rats, there is no true IL-8 gene; related chemokines such as CXCL1 and CXCL2 perform analogous roles in neutrophil recruitment.

Clinical significance of IL-8 includes elevated levels in sepsis, pneumonia, chronic inflammatory diseases, and several cancers, where it is associated with disease severity and progression. Therapeutic approaches targeting IL-8 or its receptors have been explored in clinical trials but have not resulted in widely approved IL-8–specific therapies.