Involvement of the Rho kinases in mediating sepsis.

Abstract

Acute lung injury (ALI) is a serious complication that develops from a variety of conditions that include severe influenza infections, blood transfusions and severe sepsis (1-3). An individual with sepsis is associated with a 40% increased risk of developing ALI over other etiologies that contribute to ALI (4). Acute lung injury manifests itself clinically in a similar manner despite the underlying cause and can be treated in the same way for most of these etiologies (2). ALI is divided up into the following three phases: i)exudative, ii) proliferative and iii) fibrotic (5). The exudative phase is characterized by cytokine production that increases inflammation in the lung. As well the cytokine production leads to increases in oxidative stress and protease activity (2). There is a rapid onset of respiratory failure leading to arterial hypoxemia that is refractory towards oxygen supplementation (4). The hallmark of the exudative phase is the infiltration of protein rich fluid from the vasculature into the alveolar space. This movement of fluid can lead to alveolar flooding where by the removal of water and protein rich exudate is impaired. This results in decreased lung compliance due to increased viscosity from the protein rich exudates, neutralization of alveolar surfactant and a decrease in the production of surfactant from type II pneumocytes. This leads to an increase in alveolar dead space where gas exchange is impaired (5). In addition to the protein rich fluid accumulation in the alveoli there is an increase in activated neutrophil infiltration. Neutrophil derived elastase has been shown to damage both alveolar epithelial cells and lung endothelial cells (2).