Leukotriene Receptor Antagonists

Marzena E. Krawiec, MD, Nizar J. Jarjour, MD


Semin Respir Crit Care Med. 2002;23(4) 

In This Article

Anti-Inflammatory Properties of the LTRAs

Studies have suggested that inhalation of cysLT results in an influx of inflammatory cell types including eosinophils, predominantly, but also neutrophils, basophils, and lymphocytes. The ability of the LTRAs to block such inflammatory reactions has been demonstrated in several animal models.[73,74] In vitro, eosinophils from patients with mild asthma pre-incubated with montelukast for 15 minutes demonstrated inhibition of transmigration through cultured human umbilical vein endothelial cell monolayers in response to platelet activating factor, a potent eosinophil chemoattractant.[75] Similar anti-inflammatory effects of these drugs have been demonstrated in humans. BAL basophil and lymphocyte numbers were significantly reduced 48 hours following SAC in 11 mild to moderate asthmatics treated with zafirlukast (20 mg b.i.d. for 1 week) compared with placebo (p < 0.01).[41] Sputum and blood eosinophil counts were diminished by 50% in 40 mild adult asthmatics treated with montelukast (10 mg daily) for 4 weeks.[76] These sputum and blood findings correlated with clinical improvements such as improved asthma symptoms and decreased beta2-agonist use. Similarly, declines in bronchial tissue eosinophilia have been demonstrated with both montelukast[77] and pranlukast.[78] Finally, reductions in peripheral blood eosinophils have also been reported with chronic dosing of the LTRAs.[79,80] Conversely, although treatment with montelukast 10 mg 36 and 12 hours pre- and 12 hours post-challenge) provided significant protection against both the allergen-induced early and late airway responses in 12 mild allergic asthmatics, there was no change in sputum eosinophil percentage or activity.[34] Potentially, this lack of suppression may have been related to the short duration of pretreatment suggesting that more chronic dosing may be required to reveal specific anti-inflammatory effects. Overall, these studies suggest that LTs may contribute varying amounts to bronchoconstriction and inflammation in different asthmatic subjects. Therefore the clinical response of asthmatic patients treated with LTRA drugs may also vary due to the heterogeneous nature of the disease.


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