Inflammatory processes during acute respiratory distress syndrome: a complex system

• Published in: Current opinion in critical care Vol. 24; no. 1; p. 1
• Main Authors: Reiss, Lucy K, Schuppert, Andreas, Uhlig, Stefan
• Format: Journal Article
• Language: English
• Published: United States 01.02.2018
• Subjects: Apoptosis - physiology; Autophagy - physiology; Cytokines - immunology; Gene Expression Profiling; Humans; Inflammasomes - physiology; Inflammation - genetics; Inflammation - pathology; Inflammation - physiopathology; Inflammation - therapy; Respiratory Distress Syndrome, Adult - genetics; Respiratory Distress Syndrome, Adult - pathology; Respiratory Distress Syndrome, Adult - physiopathology; Respiratory Distress Syndrome, Adult - therapy; Systems Theory
• ISSN: 1531-7072
• DOI: 10.1097/mcc.0000000000000472

ARDS is a severe pulmonary disease characterized by inflammation. However, inflammation-directed therapies have yet failed to improve the outcome in ARDS patients. One of the reasons may be the underestimated complexity of inflammation. Here, we summarize recent insights into the complex interrelations between inflammatory circuits. Gene expression analysis from animal models or from patients with ARDS, sepsis or trauma show an enormous number of differentially expressed genes with highly significant overlaps between the various conditions. These similarities, however, should not obscure the complexity of inflammation. We suggest to consider inflammation in ARDS as a system controlled by scale-free networks of genome-wide molecular interaction with hubs (e.g. NFκB, C/EBPβ, ATF3), exhibiting nonlinear emergence and the ability to adapt, meaning for instance that mild and life-threatening inflammation in ARDS are distinct processes. In order to comprehend this complex system, it seems necessary to combine model-driven simulations, data-driven modelling and hypothesis-driven experimental studies. Recent experimental studies have illustrated how several regulatory circuits interact during pulmonary inflammation, including the resolution of inflammation, the inflammasome, autophagy and apoptosis. We suggest that therapeutic interventions in ARDS should be based on a systems approach to inflammation.