title: Effects of budesonide on the lung functions, inflammation and apoptosis in a saline-lavage model of acute lung injury.
abstract: Diffuse alveolar injury, edema, and inflammation are fundamental signs of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Whereas the systemic administration of corticosteroids previously led to controversial results, this study evaluated if corticosteroids given intratracheally may improve lung functions and reduce edema formation, migration of cells into the lung and their activation in experimentally-induced ALI. In oxygen-ventilated rabbits, ALI was induced by repetitive saline lung lavage, until PaO2 decreased to < 26.7 kPa in FiO21.0. Then, one group of animals was treated with corticosteroid budesonide (Pulmicort susp inh, AstraZeneca; 0.25 mg/kg) given intratracheally by means of inpulsion regime of high-frequency jet ventilation, while another group was non-treated, and both groups were oxygen-ventilated for following 5 hours. Another group of animals served as healthy controls. After sacrifice of animals, left lung was saline-lavaged and protein content was measured and cells in the lavage fluid were determined microscopically. Right lung tissue was used for estimation of edema formation (expressed as wet/dry weight ratio), for histomorphological investigation, immunohistochemical determination of apoptosis of lung cells, and for determination of markers of inflammation and lung injury (IL-1β, IL-6, IL-8, TNF-α, IFNγ, esRAGE, caspase-3) by ELISA methods. Levels of several cytokines were estimated also in plasma. Repetitive lung lavage worsened gas exchange, induced lung injury, inflammation and lung edema and increased apoptosis of lung epithelial cells. Budesonide reduced lung edema, cell infiltration into the lung and apoptosis of epithelial cells and decreased concentrations of proinflammatory markers in the lung and blood. These changes resulted in improved ventilation. Concluding, curative intratracheal treatment with budesonide alleviated lung injury, inflammation, apoptosis of lung epithelial cells and lung edema and improved lung functions in a lavage model of ALI. These findings suggest a potential of therapy with inhaled budesonide also for patients with ARDS.
authors.affiliation: Biomedical Center Martin and Department of Physiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia. mokra@jfmed.uniba.sk.
authors.forename: D
authors.initials: D
authors.lastname: Mokra
authors.affiliation: Biomedical Center Martin and Department of Physiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.
authors.forename: P
authors.initials: P
authors.lastname: Kosutova
authors.affiliation: Department of Histology and Embryology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.
authors.forename: S
authors.initials: S
authors.lastname: Balentova
authors.affiliation: Department of Histology and Embryology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.
authors.forename: M
authors.initials: M
authors.lastname: Adamkov
authors.affiliation: Biomedical Center Martin and Department of Physiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.
authors.forename: P
authors.initials: P
authors.lastname: Mikolka
authors.affiliation: Biomedical Center Martin and Department of Pharmacology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.
authors.forename: J
authors.initials: J
authors.lastname: Mokry
authors.affiliation: Biomedical Center Martin and Department of Physiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.
authors.forename: M
authors.initials: M
authors.lastname: Antosova
authors.affiliation: Biomedical Center Martin and Department of Physiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia.
authors.forename: A
authors.initials: A
authors.lastname: Calkovska
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000378:metabolism; D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D019819:Budesonide / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D004487:Edema / Q000188:drug therapy / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014691:Ventilation / Q000379:methods
chemical_list: D000305:Adrenal Cortex Hormones; D015415:Biomarkers; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D019819:Budesonide; D053148:Caspase 3; D010100:Oxygen