Does Epigenetic Regulation Plays a Critical Role in Acute Lung Injury?

Acute lung injury and the acute respiratory distress syndrome (ALI/ARDS) are severe respiratory conditions that remain as significant public health concerns, with ARDS mortality as high at 30-40% [1-4]. ALI/ARDS is primarily caused by pneumonia, it is also caused by a variety of other clinical disorders including pulmonary or non-pulmonary sepsis, major trauma, inhalation injury such as aspiration of gastric or oropharyngeal contents, drug over use, and blood products. ALI/ARDS features with widespread damage to the various types of cells in the lung and the structures of alveolar capillary membrane. The pathogenesis of ALI/ARDS involves three major overlapping phases, inflammatory phase, proliferative phase, and fibrotic phase. Pathological stimuli cause cytokine secretion and inflammatory cell infiltration to the injured site followed by the activation of pro-inflammatory mediator cascades. Many proinflammatory mediators including pro-inflammatory cytokines and chemokines are involved in the pathogenesis of ALI/ARDS. Increased amount of TNF-α, IL-1β, IL-6, and IL-8 are reported in BAL fluid and plasma of patients with ARDS, orchestrating with the low levels of inflammatory inhibitors such as IL-1α, IL-4, and IL-10. Inflammation in ALI/ARDS results in cell death, alveolar epithelial membrane leaking, and dysfunction of surfactant secretion. The followed injury repair mediates fibro proliferative response further impaired lung function.