TY - JOUR T1 - Species comparison of interleukin-13 induced airway hyperreactivity as model for allergic asthma JF - European Respiratory Journal JO - Eur Respir J VL - 44 IS - Suppl 58 SP - P1783 AU - Olga Danov AU - Sharon Melissa Jimenez Delgado AU - Helena Drake AU - Olaf Pfennig AU - Christine Förster AU - Armin Braun AU - Katherina Sewald Y1 - 2014/09/01 UR - http://erj.ersjournals.com/content/44/Suppl_58/P1783.abstract N2 - High effort has been put into development of new therapeutic targets for allergic asthma. Currently there is a need for translational models with improved predictivity in respect to efficacy and safety. Interleukin (IL)-13 as a key cytokine of asthma is widely used to induce airway hyperreactivity in laboratory rodents. Moreover, based on the disease model an ex vivo tissue model of precision-cut lung slices (PCLS) can be used for pre-clinical studies to evaluate the efficacy of new biopharmaceuticals.PCLS were prepared from Balb/c mice, Brown Norway rats, and humans. Airways were pre-incubated with 100 ng/mL IL-13 of the corresponding species. Subsequently, bronchoconstriction was induced by addition of methacholine (MCh) and visualized by videomicroscopy. IL-13 receptor was stained in the airways of mouse, rat and human PCLS by immunohistochemistry.MCh-induced bronchoconstriction in mouse and rat PCLS exhibited an EC50 of 80nM and 220nM, respectively. Pre-incubation with IL-13 decreased EC50 to 50 nM (mouse) and 170 nM (rat). Human IL-13 induced hyperreactivity resulted in decreased EC50 values of 47 nM compared to 180 nM of control. In general, pre-incubation of PCLS in the presence of IL-13 resulted in all species in stronger bronchoconstriction at maximum MCh concentration and hyperreactivity compared to untreated tissue. IL-13 receptor was present in PCLS of all species.This study shows that PCLS of rodent and human can be used to mimic IL-13 induced airway hyperreactivity in lung tissue. From all tested species human PCLS showed best results to mimic airway hyperreactivity. In future studies, PCLS can be used for pre-clinical studies to evaluate the antagonist efficacy. ER -