The potential of neutrophil elastase inhibitors as anti-inflammatory therapies

Therapeutic inhibition of neutrophil-derived elastases holds promise with powerful treatment effects observed in various preclinical models of lung, bowel and skin inflammation and ischaemia-reperfusion injury relevant to myocardial infarction, stroke and transplant medicine.This brief review considers recent studies eliciting the complex interaction between neutrophil-derived elastases and endogenous inhibitors that determines elastase-mediated inflammation in humans. Translating results of preclinical studies with neutrophil elastase inhibitors remains challenging. Future clinical studies will harness developments in drug delivery and utilize more specific markers of neutrophil elastase activity to inform on the efficacy of inhibition. A summary of recently published and ongoing clinical trials with synthetic inhibitors sivelestat and AZD9668 and recombinant elafin is provided.Clinical trials with neutrophil elastase inhibitors in lung and cardiovascular disease are ongoing, and future studies will incorporate novel delivery approaches and be directed by specific markers of neutrophil-derived elastase activity to target inhibition to the sites of inflammatory tissue injury.