title: Deactivation of alveolar macrophages in septic neutropenic ARDS.
abstract: OBJECTIVE
  Neutrophils often have been involved in the pathophysiology of ARDS. However, authentic ARDS has been described in patients with severe neutropenia, suggesting the presence of other potential mechanisms that are responsible of this syndrome. Alveolar macrophages (AMs) could be involved in the development of ARDS, and so we decided to study AM activation in neutropenic patients.
  
  
  METHODS
  We designed a prospective study and enrolled two subgroups of consecutive patients (group A, 18 patients; group B, 22 patients) with septic ARDS. In the first period, 7 of 18 patients were neutropenic, and in the second period 10 of 22 patients were neutropenic. All neutropenic patients were treated with granulocyte colony-stimulating factor (G-CSF).
  
  
  RESULTS
  In group A, BAL fluid samples were analyzed for differential and total cell counts, and alveolar activation marker expression (ie, human leukocyte antigen [HLA]-DR locus) was determined. Basal and lipopolysaccharide (LPS)-stimulated production of tumor necrosis factor, interleukin (IL)-1 beta, IL-6, and IL-10 was evaluated in group B. In neutropenic patients, the BAL fluid total cell count and the neutrophil absolute count was significantly lower compared to those in nonneutropenic patients (p = 0.029 and p = 0.046, respectively). HLA-DR expression on AMs was significantly decreased (p = 0.016), and the percentage of AMs expressing HLA-DR was also significantly lower (p = 0.041). In neutropenic patients, the mean percentage of AMs expressing HLA-DR was significantly lower in deceased patients compared to survivors (30 +/- 7 vs 43 +/- 1, respectively; p = 0.047). Basal AMs released cytokines was comparable between the two groups; however, LPS stimulation yielded a deactivation of AMs in neutropenic patients.
  
  
  CONCLUSIONS
  These results suggest a deactivation and/or hypoactivation of AMs in septic ARDS patients. This deactivation/hypoactivation could be linked to the use of G-CSF as this molecule has been shown to generate a down-regulation of HLA-DR expression.
authors.affiliation: Department of Anesthesiology and Intensive Care Unit, Paoli-Calmette Institute, Marseille, France. mokartd@marseille.fnclcc.fr
authors.forename: Djamel
authors.initials: D
authors.lastname: Mokart
authors.forename: Benoit P
authors.initials: BP
authors.lastname: Guery
authors.forename: Reda
authors.initials: R
authors.lastname: Bouabdallah
authors.forename: Claude
authors.initials: C
authors.lastname: Martin
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Blache
authors.forename: Christine
authors.initials: C
authors.lastname: Arnoulet
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mege
mesh_terms: D000328:Adult; D000368:Aged; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000150:complications / Q000188:drug therapy / Q000401:mortality; D011379:Prognosis; D011446:Prospective Studies; D012128:Respiratory Distress Syndrome / Q000150:complications / Q000401:mortality / Q000503:physiopathology
chemical_list: D016207:Cytokines; D006684:HLA-DR Antigens; D016179:Granulocyte Colony-Stimulating Factor