Acute Respiratory Distress Syndrome (ARDS) is an inflammatory condition that leads to acute hypoxic respiratory failure requiring mechanical ventilation. The causes of ARDS are heterogenous and include diseases such as sepsis and COVID-19. Despite the significant mortality and morbidity associated with ARDS no specific pharmacological interventions have been developed. We have identified that approximately 30% of ARDS patients have high levels of serum ferritin which correlate with increased mortality. Hyperferritinaemia also correlates with increased inflammatory cytokines and tissue damage, suggesting a specific inflammatory signature is associated with high ferritin levels. Inflammasomes are highly proinflammatory signalling complexes that drive the production of IL-1b and IL-18 as well as lytic cell death called pyroptosis. This project will investigate inflammasome activation in ARDS patient samples including bronchoalveolar lavage and plasma. Samples from an inhaled LPS model of human lung inflammation will also be examined. The link between hyperferritinaemia and inflammasome activation will be investigated using human macrophages and a range of immunological and cell biological approaches. This research may support the therapeutic targeting of the inflammasome pathway as a treatment for ARDS which is currently an urgent unmet medical need.
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