TY - JOUR T1 - Differential effects of simvastatin and dexamethasone on TLR3-induced anti-viral cytokines in asthmatic epithelium JF - European Respiratory Journal JO - Eur Respir J VL - 42 IS - Suppl 57 SP - P3145 AU - Angelica Brandelius AU - Irma Mahmutovic Persson AU - Jenny Calvén AU - Leif Bjermer AU - Carl Persson AU - Morgan Andersson AU - Lena Uller Y1 - 2013/09/01 UR - http://erj.ersjournals.com/content/42/Suppl_57/P3145.abstract N2 - Possibly reflecting anti-inflammatory properties, statin treatment may ameliorate viral-induced exacerbations. We have shown that simvastatin but not dexamethasone inhibits viral-induced, potentially pathogenic thymic stromal lymphopoietin production. It is important that treatments of exacerbations spare the host defence to viral infections. IFN-beta, IFN-lambda and IL-32 are major antiviral components of innate immunity.Objective: Explore effects of simvastatin and dexamethasone on TLR3-induced IFN-beta, IFN-lambda and IL-32 in asthmatic epithelium.Methods: Primary bronchial epithelial cells, obtained by fibre optic bronchoscopy from allergic asthma patients (n=6) were grown in 12-well plates and treated with simvastatin (0,2-5μg), dexamethasone (1μM) or vehicle control prior to TLR3 stimulation for 3 and 24 h and samples analysed by RTqPCR and ELISA.Results: TLR3 stimulation induced early (3h) expression of IFN-beta (1000-fold) that was dose-dependently inhibited by simvastatin but not by dexamethasone. IFN-lambda was induced (6000-fold) at 3h and further sustained at 24 h (2000-fold). Only the early IFN-lambda expression was reduced by the highest dose of simvastatin. Dexamethasone was without effect. IL-32 was induced (2-fold) at 3h and further increased at 24h. At both time-points the highest dose of simvastatin reduced IL-32 but dexamethasone was without effect.Conclusion: Dexamethasone treatment spared TLR3-induced expression of all three anti-viral cytokines in bronchial epithelial cells from asthma donors. Simvastatin completely inhibited TLR3-induced IFN-beta whereas the inducement of IFN-lambda and IL-32 were largely spared by simvastatin. ER -