title: Protective effect of procysteine on Acinetobacter pneumonia in hyperoxic conditions.
abstract: OBJECTIVE
  Ventilator-associated pneumonia (VAP) is an important cause of morbidity and mortality in critical care settings. Acinetobacter has become a leading cause of VAP. In particular, the appearance and spread of multidrug-resistant Acinetobacter is of great concern. In this study, we examined the effect of the antioxidant procysteine on Acinetobacter murine pneumonia in hyperoxic conditions in order to simulate VAP.
  
  
  METHODS
  Acinetobacter was administered intranasally to BALB/c mice kept in hyperoxic conditions. At designated timepoints, bacterial number, cytokine production and histopathological findings in the lungs were examined. The effects of procysteine on survival rates, lung bacterial burdens and the phagocytic activities of alveolar macrophages were evaluated.
  
  
  RESULTS
  Drastic decreases in survival were observed when the infected mice were kept in hyperoxic conditions (P < 0.001). Significant differences in pulmonary bacterial number and neutrophil accumulation were observed between mice kept in hyperoxic or normoxic conditions on day 3. Although all mice infected with Acinetobacter spp. and kept in hyperoxic conditions died by day 3, procysteine treatment significantly improved survival (60% survival on day 7, P < 0.01). Procysteine treatment decreased the lung bacterial burden on days 2 and 3. Finally, improved uptake of FITC-labelled beads by alveolar macrophages from mice treated with procysteine and kept in hyperoxic conditions was noted.
  
  
  CONCLUSIONS
  These results suggest that hyperoxia increases mortality in mice with Acinetobacter pneumonia and that procysteine improves survival by increasing the phagocytic activity of alveolar macrophages in mice kept in hyperoxic conditions.
authors.affiliation: Department of Microbiology and Infectious Diseases, Toho University School of Medicine, Tokyo 143-8540, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Saito
authors.forename: Soichiro
authors.initials: S
authors.lastname: Kimura
authors.forename: Tomoo
authors.initials: T
authors.lastname: Saga
authors.forename: Yoshi
authors.initials: Y
authors.lastname: Misonoo
authors.forename: Sadako
authors.initials: S
authors.lastname: Yoshizawa
authors.forename: Yoshikiyo
authors.initials: Y
authors.lastname: Akasaka
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Ishii
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kuwano
authors.forename: Keizo
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tateda
mesh_terms: D000151:Acinetobacter Infections / Q000517:prevention & control*; D000281:Administration, Intranasal; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D058491:Bacterial Load; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D006651:Histocytochemistry; D008168:Lung / Q000473:pathology; D016676:Macrophages, Alveolar / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis; D053717:Pneumonia, Ventilator-Associated / Q000517:prevention & control*; D011761:Pyrrolidonecarboxylic Acid / Q000008:administration & dosage*; D053778:Thiazolidines / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000975:Antioxidants; D016207:Cytokines; D053778:Thiazolidines; D011761:Pyrrolidonecarboxylic Acid; C029536:2-oxothiazolidine-4-carboxylic acid
keywords: VAP; alveolar macrophages; phagocytic activity; ventilator-associated pneumonia