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Disclosure of conflict of interest None to declare.""Acute respiratory distress syndrome (ARDS), with approximately 200,000 annual cases in the United States, is one of the leading causes of death in young adults and a major Chlormezanone concern in victims of combat trauma in the military [1]. The accompanying cost for each case is roughly $150,000 [2]. The pathophysiology of ARDS causes death in 30-60% of affected patients, despite treatment with the standard of care low tidal volume (LTV) ventilation strategy [3]. Diagnostically, the principal feature of ARDS, according to the 2011 ESICM ��Berlin�� definition, is a PaO2/FiO2 ratio of less than 300 mmHg. Additionally, respiratory symptoms must be new (selleck mechanical trauma delivered to lung tissue by inappropriate mechanical ventilation, which our group has shown to be critical in ARDS pathogenesis [1,2]. Unchecked inflammation causes barrier failure and subsequent accumulation of fluid in the alveoli of the lungs, leading to reduced gas exchange [4]. ARDS poses a significant challenge for the clinician and to our knowledge, there are no medications approved by the U. S. Food and Drug Administration to treat this condition. By the time ARDS appears, the current standard of care treatment is only supportive in the form of mechanical ventilation, which is only minimally effective [3]. Furthermore, mechanical ventilation, while necessary in the short term, contributes to ARDS pathology via a secondary, ventilator-induced lung injury (VILI), thus significantly increasing mortality [5]. The lack of insight into the complex workings of http://www.selleckchem.com/products/azd5363.html the human acute inflammatory response has been a primary obstacle for developing effective treatments for ARDS. The inflammatory response comprises dynamic networks that can include hundreds of mediators derived from multiple cell types, all of which vary over time. Most variables are interrelated due to the feedback structure of the system, and this complexity is compounded by frequent pleiotropy and redundancy, as well as the multiscale aspect inherent in a system that affects multiple tissues and organs. The traditional reductionist experimental approach, in which a single variable is isolated and its role inferred from the results, has been insufficient in elucidating the workings of this system.