Journal Article

Multi-pronged inhibition of airway hyper-responsiveness and inflammation by lipoxin A sub(4)

De Sanctis, GT, Schmidt, BA, Drazen, J M, Szczeklik, W, Kim, E, Serhan, C N, Levy, B D, Ackerman, K, Devchand, PR

2002

Overview

The prevalence of asthma continues to increase and its optimal treatment remains a challenge. Here, we investigated the actions of lipoxin A sub(4) (LXA sub(4)) and its leukocyte receptor in pulmonary inflammation using a murine model of asthma. Allergen challenge initiated airway biosynthesis of LXA sub(4) and increased expression of its receptor. Administration of a stable analog of LXA sub(4) blocked both airway hyper-responsiveness and pulmonary inflammation, as shown by decreased leukocytes and mediators, including interleukin-5, interleukin-13, eotaxin, prostanoids and cysteinyl leukotrienes. Moreover, transgenic expression of human LXA sub(4) receptors in murine leukocytes led to significant inhibition of pulmonary inflammation and eicosanoid-initiated eosinophil tissue infiltration. Inhibition of airway hyper-responsiveness and allergic airway inflammation with a stable LXA sub(4) analog highlights a unique counter-regulatory profile for the LXA sub(4) system and its leukocyte receptor in airway responses. Moreover, our findings suggest that lipoxin and related pathways offer novel multi-pronged therapeutic approaches for human asthma.