TY - JOUR T1 - Antioxidant supplementation attenuates changes in innate immunity associated with diesel exhaust (DE) in the lung: A controlled crossover exposure study JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - 3443 AU - Chris Carlsten AU - Mandy Pui AU - Meaghan MacNutt AU - John Lay AU - Neil Alexis Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/3443.abstract N2 - Rationale: Oxidative stress is thought to induce negative health effects associated with exposure to DE and may result from altered innate immunity. Therefore, anti-oxidant supplementation may modify DE-related changes in phagocytosis in airways.Methods: 12 participants (4 mild asthmatics and 8 healthy controls) completed a double-blinded, randomized, crossover, counter-balanced study of 3 exposure conditions, each separated by a 2-wk washout period: (1) DE (300ug PM2.5/m3 for 2 hours) with anti-oxidant (N-acetylcysteine 600mg 3x/day for 5 days preceding, and on the day of the exposure) [“DEN”], (2) DE with placebo [“DEP”], or (3) filtered air with placebo [“FAP”]. Induced sputum was collected 6 hours after each exposure. Sputum neutrophils and macrophages were analyzed by flow cytometry for changes in innate immune response (phagocytosis). Those with PC20≤8 were defined as “reactive” and those with PC20>8 as “non-reactive”.Results: Phagocytosis in sputum macrophages was greater after DEP than after FAP (mean phagocytosis units = 22.8 and 15.8, respectively) and this difference was attenuated by DEN (mean phagocytosis units = 17.8 units). 6 subjects were methacholine-reactive at baseline; reactivity status did not modify phagocytosis.Conclusions: DE-associated increase in phagocytosis in human airways appears mitigated by anti-oxidant supplementation (N-acetylcysteine). The suggestion that DE upregulates the innate immune response in sputum macrophages, and that this is mediated by oxidative stress, parallels novel data from our lab regarding changes in airway reactivity to methacholine in response to FAP, DEP, and DEN. ER -