Recent developments in COPD

printing supported by . Visit Chiesi at Stand D.30 SUNDAY, SEPTEMBER 25TH 2011 Methods: Forty 3-months old Wistar rats were randomized into 4 groups. Control group (group 1) was injected intratracheally 0,4 ml of normal saline, other animals (groups 2-4 ) received one intratracheal injection of 20 units (U) porcine pancreatic elastase in 0,4 ml of saline. Next day (group 2) and 7 day (group 4) rats were intravenously injected 2000000 autologous MSCs in 0,5 ml of saline. Group 4 was used as emphysema control. Before killing on 21-st day rats were undergone peritoneal lavage with analysis of hemi-luminescent macrophages activity in the obtained fluid Results: The lungs of groups 2-4 had various degrees of centriacinar emphysema. There were no significant differences between the sizes of dilated respiratory bronchioles in groups 2 & 4. Only in the 2-nd group we observed the lymphoid infiltration around arterioles. The width of respiratory bronchioles in group 3 was on 41% less than in the 4-th. The Index of hemi-luminescent MA has made 28,8±1,1 U (1 group), 35,8±1,6 U (2 group), 31,9±1,9 U (group 3), 57,3±1,3 U (group 4). Conclusions: MSCs have various effects on damaged lung tissue at different periods of transplantation. MSCs can enhance the local vascular inflammatory response in the early period of elastase injury. More later injection of MSCs can repair the structure of acini in acute model of emphysema in rats. P419 IL-10 resolves the neutrophilic inflammation in mice exposed to cigarette smoke Manabu Higaki1, Hiroo Wada1, Tetsuo Yasutake1, Shinichiro Mikura1, Kojiro Honda1, Masuo Nakamura1, Mamoru Niikura2, Fumie Kobayashi2, Shigeru Kamiya2, Hajime Goto1. 1Department of Respiratory Medicine, Kyorin University School of Medicine, Tokyo, Japan; 2Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo, Japan Introduction: IL-10 plays a suppressive role in the inflammation. In order to elucidate the role of IL-10 in the inflammation caused by cigarette smoke, mice exposed to cigarette smoke were investigated. Materials & methods: Mice (C57BL/6J) were exposed either to cigarette smoke or to environmental air for 5, 8 or 12 days. To characterize the inflammation, cellularity in bronchoalveolar lavage (BAL) fluid was investigated. The levels of inflammation-associated cytokines, such as IL-10, KC, MIP-2, TNF-a and GMCSF, were further determined by measuring both mRNA levels in the lung tissues and the protein levels in BAL fluid. Then, a group of mice was intranasally treated either with recombinant murine IL-10 or with vehicle and exposed to cigarette smoke, before the same analysis was performed. Results: Cigarette smoke exposure provoked pulmonary inflammation in mice, as neutrophil and macrophage counts in BAL fluid were increased (p<0.01). In parallel, the levels of various proinflammatory cytokines including KC and MIP-2 significantly increased (p<0.01), as well as IL-10 expression. The enhancement in the neutrophil counts in BAL fluid caused by smoke exposure was significantly attenuated by the intranasal administration of IL-10 (p<0.05), while that in macrophage counts was not altered. Conclusion: Our results suggested that IL-10 potentiates the suppression of the neutrophil-associated inflammatory reactions caused by cigarette smoke exposure. P420 Activation of the inflammasome pathway during exacerbations of COPD Patricia Sobradillo1, Rosa Faner2, Nestor Soler4, Eugeni Ballester4, Juan Ignacio Aróstegui3, Jordi Yagüe3, Juan Manel3, Alvar Agusti4. 1CIBERES, Ciberes, Barcelona, Spain; 2Fundación Caubet Cimera, Fundación Caubet Cimera, Barcelona, Spain; 3Immunology, Hospital Clinic, Barcelona, Spain; 4Thorax Institute, Hospital Clinic, Barcelona, Spain Introduction: Exacerbations of COPD (ECOPD) are characterized by a burst of inflammation. The inflammasome is an intracellular sensing mechanism that leads to activation of caspase-1 and processing of pro IL-1β and pro IL-18 into their mature forms. Aim: To investigate if the inflammasome pathway is activated in ECOPD patients. Methods: We studied 10 COPD patients hospitalized because of ECOPD, 7 of whom were revaluated 3 months after discharge (sECOPD), 13 patients with clinically stable COPD (SCOPD), 8 smokers with normal lung function (S) and 11 non smokers (NS). We determined: (1) in serum: caspase-1, IL-1β, IL-18, IL-1Ra, IL-6, IL-8 and TNF-a; (2) in circulating monocytes and lymphocytes: intracellular activity of caspase-1 (basally and after stimulation with inflammasome ligands: ATP, Nigericine and Cigarette Smoke Medium); and (3) in whole blood: caspase-1