title: Sepsis-induced lung injury and the effects of ibuprofen pretreatment. Analysis of early alveolar events via repetitive bronchoalveolar lavage.
abstract: Current knowledge of alveolar pathophysiology during early sepsis-induced acute lung injury (ALI) and the role of resident alveolar macrophages (AM) in mediating alveolar inflammatory events during sepsis is limited. Further, the effects of ibuprofen pretreatment upon alveolar pathophysiology and AM function during early sepsis-induced ALI is unclear. Utilizing repetitive bronchoalveolar lavage (BAL) in a porcine model of sepsis-induced ALI, we studied changes in alveolar cellular constituents, BAL protein content and molecular composition, and AM superoxide anion (O2-.) generation during early sepsis. The neutrophil percentage of recovered alveolar cells (17 +/- 8%, t = 300 min versus 2 +/- 1%, t = 0; p = 0.06) and the bronchoalveolar lavage total protein content (493 +/- 110 micrograms/ml, t = 300 min versus 109 +/- 18 micrograms/ml, t = 0; p less than 0.05) increased in septic animals. Increases in BAL fluid total protein were primarily due to low-molecular-weight plasma protein, indicating relative preservation of alveolar-capillary membrane size selectivity. Alveolar macrophages harvested following 300 min of sepsis generated significantly less O2-. following phorbol myristate acetate (PMA) stimulation compared to AM harvested at baseline. Ibuprofen pretreatment of septic animals completely blocked leakage of plasma proteins into the alveoli and attenuated neutrophil migration but did not prevent downregulation of AM O2-. generation. Increased alveolar-capillary membrane permeability, neutrophil migration into the alveoli, and downregulation of AM oxidant generation occur within hours of the onset of sepsis. Ibuprofen pretreatment significantly attenuates early sepsis-induced ALI without altering sepsis-induced AM dysfunction.
authors.affiliation: Department of Internal Medicine, Virginia Commonwealth University Medical College of Virginia, Richmond.
authors.forename: J K
authors.initials: JK
authors.lastname: Jenkins
authors.forename: P D
authors.initials: PD
authors.lastname: Carey
authors.forename: K
authors.initials: K
authors.lastname: Byrne
authors.forename: H J
authors.initials: HJ
authors.lastname: Sugerman
authors.forename: A A
authors.initials: AA
authors.lastname: Fowler
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000473:pathology; D015633:Extravascular Lung Water / Q000187:drug effects; D005260:Female; D007052:Ibuprofen / Q000008:administration & dosage* / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D010100:Oxygen / Q000097:blood; D011506:Proteins / Q000032:analysis; D011552:Pseudomonas Infections / Q000150:complications*; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D013481:Superoxides / Q000378:metabolism; D013552:Swine
chemical_list: D011506:Proteins; D013481:Superoxides; D010100:Oxygen; D007052:Ibuprofen