title: Exacerbation with granulocyte colony-stimulating factor of prior acute lung injury during neutropenia recovery in rats.
abstract: OBJECTIVE
  Neutropenia recovery may be associated with an increased risk of respiratory function deterioration. A history of pneumonia complicating neutropenia has been identified as the leading cause of adult respiratory distress syndrome during neutropenia recovery in patients receiving anticancer chemotherapy, suggesting that neutropenia recovery may worsen prior lung injury.
  
  
  METHODS
  Controlled animal study.
  
  
  METHODS
  Research laboratory of an academic institution.
  
  
  METHODS
  Male Sprague-Dawley rats.
  
  
  METHODS
  We studied the effect of recovery from cyclophosphamide-induced neutropenia on endotoxin (lipopolysaccharide)- or hydrochloric acid-induced acute lung injury in rats. We also studied the effects of adding granulocyte colony-stimulating factor.
  
  
  RESULTS
  Compared with noncyclophosphamide-treated rats, rats undergoing neutropenia recovery had a higher wet/dry lung weight ratio after hydrochloric acid-induced but not lipopolysaccharide-induced acute lung injury. Granulocyte colony-stimulating factor significantly increased both alveolar cell recruitment (bronchoalveolar lavage fluid counts) and pulmonary edema (wet/dry lung ratio) in both acute lung injury models during neutropenia recovery. Furthermore, in an experiment in hydrochloric acid-instilled rats, exacerbation by granulocyte colony-stimulating factor of hydrochloric acid-induced acute lung injury was inhibited by lidocaine, which prevents adhesion of neutrophils to endothelial cells. Tumor necrosis factor-alpha and interleukin-1 beta concentrations in supernatants of lipopolysaccharide-stimulated alveolar macrophages from rats undergoing neutropenia recovery with granulocyte colony-stimulating factor treatment were significantly increased compared with rats undergoing neutropenia recovery without granulocyte colony-stimulating factor.
  
  
  CONCLUSIONS
  Neutropenia recovery can worsen acute lung injury, and this effect is exacerbated by granulocyte colony-stimulating factor.
authors.affiliation: Inserm U 492, Faculté de Médecine-Université Paris XII, Cretiel, France. elie.azoulay@creteil.inserm.fr
authors.forename: Elie
authors.initials: E
authors.lastname: Azoulay
authors.forename: Habiba
authors.initials: H
authors.lastname: Attalah
authors.forename: Kun
authors.initials: K
authors.lastname: Yang
authors.forename: Sabine
authors.initials: S
authors.lastname: Herigault
authors.forename: Hélène
authors.initials: H
authors.lastname: Jouault
authors.forename: Christian
authors.initials: C
authors.lastname: Brun-Buisson
authors.forename: Laurent
authors.initials: L
authors.lastname: Brochard
authors.forename: Alain
authors.initials: A
authors.lastname: Harf
authors.forename: Benoît
authors.initials: B
authors.lastname: Schlemmer
authors.forename: Christophe
authors.initials: C
authors.lastname: Delclaux
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D003520:Cyclophosphamide / Q000009:adverse effects; D016207:Cytokines / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects*; D006851:Hydrochloric Acid; D066298:In Vitro Techniques; D007958:Leukocyte Count; D008070:Lipopolysaccharides; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009503:Neutropenia / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D009504:Neutrophils; D011654:Pulmonary Edema / Q000139:chemically induced / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D012128:Respiratory Distress Syndrome / Q000139:chemically induced* / Q000276:immunology*; D018709:Statistics, Nonparametric
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide; D006851:Hydrochloric Acid