Role of Interleukin‐4 on Agonist Induced Airway Contraction in Mouse Lung Slices

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Asthma is a chronic disorder of the airways characterized by inflammation and airway hyper responsiveness (AHR). Interleukin‐4 (IL‐4) is released by T‐cells and mast cells in the airway and is believe to have an important role in asthma. We hypothesize that IL‐4 has a direct effect on the airway smooth muscle cells (SMCs) by increasing their contractile response to agonist such as acetylcholine (ACh). The effect of IL‐4 on airway contraction was studied in mouse lung slices with phase‐contrast microscopy. We found that the treatment of lung slices with 100 ng/ml of IL‐4 for 12 to 24 hours resulted in an increase in contraction of the airways induced by ACh as compared with the same response measured in slices treated without IL‐4 (control). However, IL‐4 treatment did not alter the sensitivity of airways to agonists as determined by the absence of a change in the concentration of ACh that produced 50% of the maximal contraction. These results suggest that IL‐4 contributes to asthma pathology by increasing airway SMC contractility. We are investigating the mechanisms underlying the increase in airway contraction induced by IL‐4 by exploring possible changes in Ca2+ signaling and other Ca2+ independent mechanisms. This study will provide useful information to develop new specific therapeutics to treat asthma.