Cysteinyl-leukotrienes contribute to sputum eosinophil chemotactic activity in asthmatics

Background: Cysteinyl-leukotrienes are lipid derived mediators involved in asthma. They are able to stimulate eosinophil chemotaxis in vitro. Induced sputum from asthmatics has been shown to contain eosinophil chemotactic activity. The purpose of our study was to evaluate the contribution of cysteinyl-leukotrienes to sputum eosinophil chemotactic activity in asthmatics and to seek whether there might be differences between asthmatics free of inhaled corticosteroids vs those regularly receiving this treatment. Methods: Twenty-two patients (11 corticosteroid free, mean FEV1 99% predicted, 11 corticosteroid-treated, mean FEV1 77% predicted) recruited from our asthma clinic underwent a sputum induction. Sputum was processed according to standard procedure. Eosinophil chemotactic activity contained in the fluid phase was assessed using Boyden microchamber model and expressed as chemotaxis index (CI). Cysteinyl-leukotrienes were measured in sputum supernatant by ELISA and their role in sputum eosionophil chemotactic activity was evaluated by using montelukast, a selective antagonist of a cys-LT1 receptor. Results: Cysteinyl-leukotrienes were well detectable in sputum supernatants from both steroid-naive (247 +/- 42 pg/ml) and steroid-treated (228 +/- 26 pg/ml) asthmatics. Sputum eosinophil chemotactic activity was indiscriminately present in both corticosteroid-naive (CI: 2.61 +/- 0.22) and corticosteroid-treated (2.98 +/- 0.35) asthmatics. Montelukast (100 mu M) significantly inhibited the eosinophil chemotactic activity in both groups achieving a mean inhibition of 54.2 +/- 9.2% (P < 0.001) and 64.7 +/- 7.8% (P < 0.001) in steroid-naive and steroid-treated asthmatics respectively. Conclusion: Cysteinyl-leukotrienes actively participate in sputum eosinophil chemotactic activity found in asthmatics irrespective of whether they are or not under treatment with inhaled corticoids.