Montelukast as a Treatment of Acute Lung Injury in Sepsis

Acute lung injury is a syndrome including acute and persistent lung inflammation with augmented vascular permeability (1). Sepsis is the most common reason for acute lung injury (2,3). The overall mortality rate of acute lung injury has been reported as 25 – 58%, although recent advances in the management of sepsis have been revealed (4,5). Many studies have pointed out the role of antiinflammatory treatments of sepsis and sepsis-induced acute lung injury. But anti-inflammatory treatments such as N-acetylcysteine and TNF-alpha blockers have still limited value in the treatment of sepsis-induced lung injury. Sepsis and its effect on lung tissue is a kind of inflammatory storm and it is therefore not easy to control all steps in this inflammatory pathway. On the other hand, the leukotriene receptor antagonist, montelukast, has been shown to ameliorate sepsis induced hepatic and intestinal injury including oxidative stress in rats (6). Montelukast has also been used as an effective agent to decrease fibrosis and oxidative stress in lungs in some animal studies (7,8). Acute lung injury due to sepsis is related to some mediators and cytokines, including fibroblastic growth factor and tumor necrosis factor (TNF-alpha), both of which are released in the inflammatory process of acute lung injury and oxidative stress (9,10). Given the multiple lines of evidence that have emerged to support a central role of leukotrienes, we hypothesize that leukotriene receptor antagonist treatment, particularly with montelukast, may reduce the fibrotic phase of acute lung injury due to sepsis. We believe that if our hypothesis is correct, a new perspective will be opened for the medical management of sepsisinduced acute lung injury. HYPOTHESIS