CHEMOKINE RECEPTOR CXCR2 ANTAGONISM TO PREVENT AIRWAYS INFLAMMATION

Neutrophilic inflammation is associated with several pulmonary conditions, including chronic obstructive pulmonary disease (CORD), severe asthma and cystic fibrosis, and contributes to disease pathophysiology. The underlying inflammation in each of these diseases is resistant to glucocorticosteroid therapy and is therefore persistent and difficult to treat. The chemokine receptor CXCR2 is highly expressed on the surface of neutrophils and has been targeted by a number of pharmaceutical companies as a potential antiinflammatory therapy. CXCR2 receptor antagonists have been shown to inhibit neutrophil accumulation in a number of preclinical models of pulmonary inflammation and show good selectivity in human cells ex vivo. Few CXCR2 receptor antagonists have been reported in clinical trials, although SCH-527123 and 58-656933 have both been shown to be effective in reducing ozone-induced airways neutrophilia in healthy volunteers. Studies are now under way in patients with CORD and preliminary data have indicated efficacy for SCH-527123. Further studies on the effects of CXCR2 receptor antagonists are required; however, they appear to be promising, novel antiinflammatory therapies for a number of pulmonary inflammatory diseases.