TY - JOUR T1 - Resveratrol impairs the release of steroid-resistant cytokines from bacterial endotoxin-exposed alveolar macrophages (AM) in COPD JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - p4102 AU - Jurgen Knobloch AU - David Jungck AU - Katja Urban AU - Andrea Koch Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/p4102.abstract N2 - Airway inflammation in COPD might be insensitive to corticosteroids. However, corticosteroids are recommended in COPD (GOLD stages III, IV) with frequent exacerbations. Resveratrol has anti-inflammatory properties and could be an alternative in COPD therapy.We investigated the effect of dexamethasone (Dex) versus resveratrol on the release of COPD-related inflammatory mediators (IL-6, IL-8, GM-CSF, MCP1) and MMP9 from AM exposed to bacterial endotoxin (lipopolysaccharide, LPS). We compared never-smokers (NS), current smokers without airway obstruction (S) and current smokers with COPD (each n=12). Cytokines and MMP9 were measured in cell culture supernatants with ELISA.The release of IL-8 and MMP9 from LPS-exposed AM was increased in COPD (each p<0.001), the release of GM-CSF and IL-6 was decreased in COPD (each p<0.01) and the release of MCP1 was without differences between the cohorts. Dex impaired the release of all cytokines and MMP9 from LPS-exposed AM of all cohorts, but for IL-8 and GM-CSF this effect was reduced in COPD (p<0.05). In AM of COPD there was an almost complete reduction of IL-6 release but only a partial reduction of IL-8, GM-CSF, MCP1 and MMP9 release demonstrating a partial corticosteroid-insensitivity. In contrast, resveratrol almost completely reduced the release of all cytokines and MMP9 without significant differences between the cohorts (Emax/COPD: 92±10%-100% reduction).Our data provide evidence for a corticosteroid-resistance of AM-dependent inflammatory responses induced by gram-negative bacteria in COPD and thus question the utility of corticosteroids in COPD therapy. Instead, resveratrol may prove an alternative. ER -