Mediators of Acute Lung Injury: A Review

Abstract

Acute lung injury and the acute respiratory distress syndrome (ARDS) are devastating illnesses with high mortality rates. ARDS is the severe end point of acute lung injury and is defined as a syndrome of inflammation and increased pulmonary vascular permeability in the absence of left heart failure. ARDS is commonly associated with trauma, sepsis, diffuse pneumonia, and shock. Anything that can diffusely injure the lung can lead to ARDS. Regardless of the origin, the pathophysiology and clinical manifestations are the same and can be divided into three phases: the acute or oxidative phase, the proliferative phase, and the fibrotic or reparative phase. Many of the clinical manifestations of acute lung injury and ARDS can be understood in the context of the inflammatory response and inflammatory mediators such as chemotactic factors and chemokines, adhesion molecules, and reactive oxygen species and proteases. The inflammatory cascade creates a response in the microvessels of the lung. Locally released inflammatory cell products damage endothelial and epithelial cells of the alveolar-capillary membrane resulting in increased permeability, release of vasoactive and additional inflammatory mediators, and recruitment of neutrophils. Neutrophils are specifically implicated in the pathogenesis of acute lung injury. The inflammatory processes involved in initiating and perpetuating acute lung injury are highly redundant and self-perpetuating. Before proliferation and repair can occur, the inflammatory process and injury must diminish. Understanding the inflammatory mediators involved in acute lung injury may result in specific therapeutic interventions.