What are leukotrienes and how do they work in asthma?

Acute asthma attacks are often triggered by allergens or exercise. Inflammatory molecules called leukotrienes are one of several substances which are released by mast cells during an asthma attack, and it is leukotrienes which are primarily responsible for the bronchoconstriction. In chronic, more severe cases of asthma, general bronchial hyperreactivity (or smooth muscle twitchiness) is largely caused by eosinophils, which are attracted into the bronchioles by leukotrienes (and other chemoattractants) and which themselves also produce leukotrienes. Thus leukotrienes seem to be critical both in triggering acute asthma attacks and in causing longer term hypersensitivity of the airways in chronic asthma.

Leukotrienes are derived from arachidonic acid, the precursor of prostaglandins. There are two families of leukotrienes. The first group acts primarily in conditions in which inflammation is dependent on neutrophils, such as cystic fibrosis, inflammatory bowel disease, and psoriasis. The second group (cysteinyl-leukotrienes) is concerned primarily with eosinophil and mast cell induced bronchoconstriction in asthma. They bind to highly selective receptors on bronchial smooth muscle and other airway tissue (Annals of Internal Medicine 1997;127:472-80).

Drugs have now been designed which can interfere with the activity of leukotrienes. Both leukotriene synthesis inhibitors and cysteinyl-leukotriene receptor antagonists have recently been shown to protect asthmatic patients against asthma attacks, but they are not useful as “rescue remedies” once an attack has already started. They act by preventing leukotriene release from mast cells and eosinophils or by blocking the specific leukotriene receptors on bronchial tissues, thus preventing bronchoconstriction, mucus secretion, and oedema. These drugs also reduce the influx of eosinophils, thus limiting inflammatory damage in the airway. These oral, non-steroidal, anti-inflammatory drugs reduce the incidence of acute asthma attacks when taken regularly.