[Physiopathology of asthma: what role for leukotrienes?]

Leukotrienes are newly formed mediators derived from arachidonic acid that are released from membrane phospholipids upon stimulation of phospholipases. As a result of their various paracrine effects, these mediators-among which the most important are leukotrienes B4, C4, D4 and E4 (LTB4, LTC4, LTD4 and LTE4, respectively)-are likely to play a central role in bronchial obstruction in asthma. Indeed, LTC4 et LTD4 act on all three effectors of bronchial obstruction, namely bronchial smooth muscle, vessels and mucus secretory cells, whereas LTB4 is a potent chemotactic factor recruiting neutrophils and, in a lesser extent, eosinophils. Urinary excretion of LTE4 is also increased during acute asthma and after bronchial provocation tests with various agonists. Increased production of leucotrienes, however, does necessarily imply they are directly involved in asthma. This is, nevertheless, likely according to results obtained from numerous clinical trials assessing the therapeutical effects of competitive antagonists of LTC4 and LTD4 and 5-lipoxygenase (5-LO) inhibitors. Pretreatment with various LTC4 antagonists and 5-LO inhibitors reduces bronchial obstruction induced by exercise, hyperventilation, aspirin and allergens. However, it is still necessary to wait for results of clinical trials looking at the effects of these drugs in a large group of individuals studied over a long period, before one can assess the real therapeutical benefit of suppressing either the production or the action of leucotrienes in asthma.