P116 Testing antioxidant and anti-inflammatory therapies in a complex lung tissue model

COPD is a disease of global importance and its primary cause airway inflammation as a consequence of cigarette smoking is well described. However, there remains a lack ofeffective therapies for this important condition. Animal models of disease are limited in their predictive utility and therefore creation of a complex, human disease modelis an important step for testing new therapeutic interventions. We therefore established a tissue model of oxidative and inflammatory responses to relevant triggers—cigarette smoke and LPS and determined the impact of interventions in the optimised system.MethodsHuman lung tissueexplants from the resected lobes of six consented patients undergoing lobectomy were used. Uniform tissue explants were established on a novel culture system and then treated with CSE and LPS before the supernatants were collected optimal dosing was determined. Treatments and control experiments were performed with the anti-oxidant Vitamin C and fluticasone. Inflammatory readouts were measured by ELISA; TNFa, IL-8 and MMP-9.ResultsLung tissue treated with CSE showed a dose-dependent increase in IL-8 and MMP-9 secretion across a range 0.6250%–20% CSE. IL-8 response to 20% CSE was 71592.21 pg/mg/ml ±4680.7 SE compared to non-stimulated tissue 14 177 pg/mg/ml ±1088 SE (n=6, p