The leukotrienes: immune-modulating lipid mediators of disease

The leukotrienes are important lipid mediators with immune modulatory and proinflammatory properties. Classical bioactions of leukotrienes include chemotaxis, endothelial adherence, and activation of leukocytes, chemokine production, as well as contraction of smooth muscles in the microcirculation and respiratory tract. When formed in excess, these compounds play a pathogenic role in several acute and chronic inflammatory diseases, such as asthma, rheumatoid arthritis, and inflammatory bowel disease. An increasing number of diseases have been linked to inflammation implicating the leukotrienes as potential mediators. For example, recent investigations using genetic, morphological, and biochemical approaches have pointed to the involvement of leukotrienes in cardiovascular diseases including atherosclerosis, myocardial infarction, stroke, and abdominal aortic aneurysm. Moreover, new insights have changed our previous notion of leukotrienes as mediators of inflammatory reactions to molecules that can fine-tune the innate and adaptive immune response. Here, we review the most recent understanding of the leukotriene cascade with emphasis on recently identified roles in immune reactions and pathophysiology.