Interleukin-8 (IL-8) (IL-8)

Interleukin-8 (IL-8), also known as CXCL8, is a pro-inflammatory chemokine that plays a central role in the recruitment and activation of neutrophils at sites of inflammation (UniProt: P10145). In the context of skin physiology, IL-8 is secreted by keratinocytes and other immune cells in response to triggers like IL-17 or TNF-alpha (PubMed: 25611158). It functions by binding to its cognate G protein-coupled receptors, CXCR1 and CXCR2, which are expressed on neutrophils and keratinocytes themselves (PubMed: 12626356). This interaction triggers signaling cascades, including the MAPK and PI3K pathways, which drive both the chemotactic movement of inflammatory cells and the accelerated proliferation of keratinocytes (PubMed: 10459516). This autocrine and paracrine loop is a hallmark of hyperproliferative skin disorders such as psoriasis, where IL-8 levels are significantly elevated (PubMed: 1711484). Consequently, therapeutic interventions targeting the IL-8 pathway, either through monoclonal antibodies like BMS-986253 or small-molecule receptor antagonists like Reparixin, are being explored to mitigate chronic inflammation and normalize epidermal growth (ClinicalTrials.gov: NCT04050462).

Other names

CXCL8Chemokine (C-X-C motif) ligand 8Neutrophil chemotactic factorNCFMonocyte-derived neutrophil chemotactic factorAMCF-IT-cell chemotactic factor

Neutralization of the IL-8 ligand or antagonism of its receptors (CXCR1 and CXCR2) to inhibit downstream signaling pathways like MAPK/ERK and PI3K/Akt, thereby reducing neutrophil infiltration and keratinocyte proliferation (PubMed: 10459516, 12626356).