15 - The Kallikrein—Kinin System in Asthma and Acute Respiratory Distress Syndrome

Abstract

The chapter reviews evidence for the involvement of kinins in asthma and the acute respiratory distress syndrome (ARDS). There is evidence that the kallikrein (KLK)–kinin system is important in chronic asthma as well as other manifestations of airway inflammation, including allergic and viral rhinitis. For many years, there have been indications that this cascade is important in the pathophysiology of acute lung injury, ARDS, and multiple-organ failure, associated with conditions such as sepsis, pancreatitis, primary pneumonia, or multiple traumas. It is unlikely that the clinical manifestations of severe and often life-threatening conditions—such as chronic asthma and acute lung injury—are due to a single mediator. There is little doubt that the KLK–kinin system is activated in these disorders and that local levels of kinins are markedly elevated in the inflammatory milieu. Thus, bradykinin (BK) and related kinins may have important roles in initiating and maintaining the pathophysiological changes that occur in the lungs. BK has deleterious, proinflammatory effects on many cell types that are mediated directly on those cells as well as by the myriad of other potentially injurious substances whose release this peptide can stimulate. Experiments in animal models of asthma and ARDS, particularly those demonstrating beneficial effects of selective kinin receptor antagonists, provide convincing testimony for a pivotal role of kinins in airway pathophysiology. Only after conducting clinical trials, utilizing kinin receptor antagonists, the roles of these endogenous peptides in human disease will become apparent.