Assistant Clinical Professor
Division of Pulmonary/Critical Care Medicine
Cedars-Sinai Medical Center

Project Title: Role of IL-1β and the NLRP3 Inflammasome in the Development of Hypoxemia in Acute Lung Injury

Moshe Arditi, MD – Cedars-Sinai Medical Center
Paul Noble, MD - Cedars-Sinai Medical Center

Multidisciplinary Expertise:
Pulmonology, Critical Care, Immunology

Project description:
Acute Respiratory Distress Syndrome (ARDS) is a clinical syndrome of acute lung injury and failure characterized by a sudden onset and a profound inability of the lungs to oxygenate the blood (hypoxemia). ARDS has a mortality rate of 30% and is responsible for 75,000 deaths annually in the United States. Despite several decades of research, we still do not understand why ARDS develops and no treatments have been found.  Interleukin 1β (IL-1β) is a potent pro-inflammatory cytokine that is implicated in the pathogenesis of ARDS; its secretion is regulated an intracellular complex termed the  NLRP3 inflammasome.  Our preliminary data in a mouse model suggests a novel role for the NLRP3 inflammasome and IL-1β specifically in the severe hypoxemia seen in ARDS.  The purpose of this investigation is to elucidate the mechanism for IL-1β dependent hypoxemia in ARDS.