Science commentary: What are leukotrienes and how do they work in asthma?

BMJ 1999;319:90 ( 10 July )

Science commentary

What are leukotrienes and how do they work in asthma?

Abi Berger, science editor.

BMJ

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

Leukotrienes are derived from arachidonic acid, the precursor of prostaglandins. There are two families of leukotrienes. Thefirst group acts primarily in conditions in which inflammationis dependent on neutrophils, such as cystic fibrosis, inflammatorybowel disease, and psoriasis. The second group (cysteinyl-leukotrienes)is concerned primarily with eosinophil and mast cell induced bronchoconstrictionin asthma. They bind to highly selective receptors on bronchialsmooth muscle and other airway tissue (Annals of Internal Medicine1997;127:472-80).

Drugs have now been designed which can interfere with the activity of leukotrienes. Both leukotriene synthesis inhibitorsand cysteinyl-leukotriene receptor antagonists have recently beenshown to protect asthmatic patients against asthma attacks, butthey are not useful as "rescue remedies" once an attack has alreadystarted. They act by preventing leukotriene release from mastcells and eosinophils or by blocking the specific leukotrienereceptors on bronchial tissues, thus preventing bronchoconstriction,mucus secretion, and oedema. These drugs also reduce the influxof eosinophils, thus limiting inflammatory damage in the airway.These oral, non-steroidal, anti-inflammatory drugs reduce theincidence of acute asthma attacks when takenregularly.