TY - JOUR T1 - Consequences of chronic pulmonary TLR9 activation in the lung and beyond JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - 4689 AU - Gillina Bezemer AU - Dmitri Fillipov AU - Esmaeil Mortaz AU - Ingrid van Ark AU - Johan Garssen AU - Aletta Kraneveld AU - Ferry Ossendorp AU - Gert Folkerts Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/4689.abstract N2 - Background: Toll like receptor 9 (TLR9) agonist CpG-ODN is being explored as an anti-allergic drug for asthma. However TLR9 could play a role in COPD. Cigarette smoke induced IL-8 production is partly TLR9 mediated.Aim: To investigate the (extra)-pulmonary effects of CpG-ODN. We hypothesized that pulmonary TLR9 activation induces neutrophil influx which could lead to adverse effects.Methods: A single dose of 0.01, 0.05 or 0.25nMol/gBW GpG-ODN was targeted to balb/c mice lungs by aspiration (acute). Next 0.01nMol/gBW GpG-ODN was administered repeatedly for 5 days (subchronic) or 5 weeks (chronic). 24 hours after last exposures, measurements were done: lung function; hypertension and heart hypertrophy; lung weight; blood and bronchoalveolar lavage (BAL) analysis; morphology of unlavaged lungs.Results: Total BAL cells were increased in all CpG-ODN mice (p<0.05). PMNs were increased in blood (30%) and BAL (39%) acute which persistent upon prolonged exposure duration. Blood lymphocytes were subchronically 19% decreased which was reflected in an abundant pulmonary (sub)- chronic lymphocyte influx. Chronic exposure leads to 21% decreased peak expiratory flow (ml/sec) and 71% increased airway resistance (cm H2O/ml/sec). Right ventricle heart hypertrophy was observed upon chronic exposure; ratio right ventricle weight/total heart weight CpG-ODN=0.23±0.007; control=0.19±0.008. Wet lung weight was 15.2% increased subchronically and 70.8% chronically.Conclusion: An interplay between neutrophils and lymphocytes could possibly play a role in TLR9 induced adverse pulmonary and cardiovascular effects. Caution is needed when CpG-ODNs are chronically administered for therapeutical purposes.Acknowledgement TIPharma D1-101 ER -