Drug discovery for neutrophil-mediated inflammation

Neutrophils are key cells of the innate immune system, the first line of defense against infection. However, neutrophils can drive a chronic inflammatory response that underlies the pathogenesis of many common diseases, including chronic obstructive pulmonary disease and inflammatory bowel disease. Despite the prominence of neutrophil-mediated inflammation in disease, there are no suitable neutrophil-targeted treatments currently available. A new report from the laboratories of Stephen Renshaw and Philip Ingham describes a novel approach for the rapid identification of compounds that can inhibit neutrophil recruitment in response to tissue injury in vivo. Using a zebrafish line in which neutrophils are labelled by GFP expression, the team screened a library of fungi-derived compounds and pinpointed a mycotoxin and a natural antibiotic with specific inhibitory effects on neutrophil migration. An in vivo imaging assay showed that the antibiotic acts independently of commonly implicated signalling pathways, suggesting an unanticipated mechanism of action. This work demonstrates that zebrafish can be used as a robust in vivo platform for high-throughput drug discovery. Page 163