Pipeline > Importance of IL-8 in COPD
COPD is a common, chronic inflammatory disease of the airways and lung parencyma, largely caused by smoking and atmospheric pollution. The inflammation is characterised by increased numbers of neutrophils, CD8+ T lymphocytes and macrophages and associated cytokines, chemokines and proteases, particularly during exacerbations. IL-8 (CXCL8), is one of the best characterised members of the chemokine family of proteins and is one of the most important neutrophil chemoattractants and activators in man. It recruits neutrophils to sites of bacterial infection and tissue injury by interacting with GAGs on endothelial cells and guides neutrophils into the underlying lung tissue.
IL-8 is increased in COPD patients (e.g. in bronchoalveolar lavage (BAL) and induced sputum), as well as in other well recognised inflammatory lung disorders, such as cystic fibrosis, steroid-resistant asthma and acute lung injury, and is particularly high during exacerbations. Once recruited into lung tissue, neutrophils augment the host defence by release of proteases and reactive oxygen species. If this recruitment is not kept in check then inflammation progresses and further lung damage results (e.g. small airway obstruction and fibrosis and emphysema).
Given the central role of IL-8 in the recruitment of neutrophils into the lung, targeting IL-8 and its two GPCR receptors CXCR1 and CXCR2 is an accepted approach among global pharmaceutical companies (including GSK and Merck Inc.) and biotech companies. It is hoped that an effective way of down-regulating the IL-8:CXCR1/2 interaction would lead to less chronic and acute infiltration of neutrophils to the lung, and better patient outcomes.