Cysteinyl leukotriene interactions with other mediators and with glucocorticosteroids during airway inflammation

Unexpected aspects of the antiasthmatic efficacy of leukotriene modifiers and glucocorticosteroids have been observed. For both classes, the observed effects may be partially explainable on the basis of underrecognized interactions involving leukotrienes. This review examines the interactions between leukotrienes and other mediators of asthma. It details the effects of glucocorticosteroids on leukotriene synthesis and on leukocyte populations in asthmatic airways. Unexpected controller effects of the leukotriene modifiers may reflect the fact that leukotrienes and other mediators of asthma, such as T_H2 cytokines, positively influence each other's generation. The ability of the leukotriene modifiers to disrupt such extensive interactions means that other relevant mediators are targeted indirectly by leukotriene blockade. Among asthma therapies, the glucocorticosteroids have numerous anti-inflammatory activities, but their effects may be unpredictable. Many processes involved in inflammation appear to escape modulation by glucocorticosteroids, including leukotriene synthesis, and leukotriene generation is among them. Understanding whether glucocorticosteroids reduce cysteinyl leukotriene levels in the airway is important in determining the clinical value of combining glucocorticosteroid therapy with leukotriene modifier therapy.