IL-13 induced asthma model in human precision-cut lung slices

Novel therapeutic treatments are required for patients suffering from chronic respiratory diseases. Rodent model reflect some features of allergic asthma, however, human physiology is missing. To reduce animal testing and to overcome limitation of rodent models human precision-cut lung slices (PCLS) were chosen as an ex vivo tissue model. To mimic features of allergic asthma, e.g., airway immune response, mucus hypersecretion and airway hyperresponsiveness, human PCLS were stimulated with interleukin (IL)-13. PCLS were prepared from human lungs and incubated with IL-13 for induction of inflammation, mucus production as determined by ELISA. IL-13-induced bronchoconstriction was measured after methacholine (MCh) provocation and visualized by videomicroscopy. Specificity was proven by usage of IL-13 antagonists. Human IL-13 induced the secretion of eotaxin-3 and TARC. Both cytokine were blocked by addition of inhibitors (anti-IL-13 or anti-IL-4R-alpha chain). Human IL-13 induced mucus hypersecretion (2-fold compared to control) in bronchial tissue. Strikingly, airway hyperreactivity was induced here demonstrated by decreasing EC50 values for MCh from 180 nM to 47 nM and by an increase in maximal bronchoconstriction. This study shows that human tissue mimics features of airway immune response, mucus hypersecretion and airway hyperreactivity, which can be used for drug development and preclinical testing.