[6] IL-8 is initially produced as a precursor peptide of 99 amino acids which then undergoes cleavage to create several active IL-8 isoforms.

In target cells, IL-8 induces a series of physiological responses required for migration and phagocytosis, such as increases in intracellular Ca2+, exocytosis (e.g. histamine release), and the respiratory burst.

The genes encoding this and the other ten members of the CXC chemokine family form a cluster in a region mapped to chromosome 4q.

[12] This process allows the build up of proteolytic enzymes and reactive oxygen species (ROS) which are necessary to break down the ECM and basement membrane.

Once the neutrophil is rolling along the endothelium, it will come into contact with a IL-8 molecule expressed on the surface which stimulates the cell signalling pathway, mediated through a G-coupled-protein-receptor.

The chemoattractant activity of IL-8 in similar concentrations to vertebrates was proven in Tetrahymena pyriformis, which suggests a phylogenetically well-conserved structure and function for this chemokine.

[19] IL-8 has also been implied to have a role in colorectal cancer by acting as an autocrine growth factor for colon carcinoma cell lines[20] or the promotion of division and possible migration by cleaving metalloproteinase molecules.

[21] It has also been shown that IL-8 plays an important role in chemoresistance of malignant pleural mesothelioma by inducing expression of transmembrane transporters.

In a 2013 study, diazepam, 4′-chlorodiazepam and flunitrazepam markedly reduced NECA-induced IL-8 production in that order of potency, whereas clonazepam showed only a modest inhibition.

[27] An increase in IL-8 levels has also been observed in relation to bronchiolitis, a common respiratory tract disease caused by viral infection.

Several cytokines and biochemical substances act as inducers of IL-8, including IL-1α, IL-1β, IL-7, IL-17, IL-22, tumor necrosis factor-alpha (TNF-α), histamine, stromal cell-derived factor-1 (SDF-1, CXCL12), lipopolysaccharides (LPSs), reactive oxygen species (ROS), cadmium (Cd), phytohemagglutinin (PHA), prostaglandin E2 (PGE2), polyinosinic-polycytidylic acid (poly I:C), concanavalin A (ConA), NaCl, thrombin, all-trans-retinoic acid (ATRA), and various other cellular stressors.

[25] Conversely, several cytokines and compounds demonstrate the ability to reduce IL-8 levels, including IL-4, IL-10, IL-35, transforming growth factor-beta 1 (TGF-β1), interferon-alpha (IFN-α), interferon-beta (IFN-β), glucocorticoids (GCs), lipoxins, vitamin D, lipoxygenase (LOX) inhibitors, antcin K, tannins, glycyrrhizin (GL), and N-acetylcysteine (NAC).

This translational control of IL-8 expression is dependent on AU-rich proximal sequences (APS), which are found in the 3' untranslated region (3' UTR) of IL-8 immediately after the stop codon.

[33] Notably, genetic polymorphisms in the CXCL8 gene can influence its transcriptional activity, potentially altering IL-8 production and contributing to variations in disease susceptibility, progression, and severity among individuals.