Modulation of neutrophil apoptosis by granulocyte colony-stimulating factor and granulocyte/macrophage colony-stimulating factor during the course of acute respiratory distress syndrome

OBJECTIVE: To determine whether bronchoalveolar lavage fluid (BALF) from patients either at risk for the acute respiratory distress syndrome (ARDS) or with sustained ARDS modulates neutrophil apoptosis; to measure the BALF concentrations of the apoptosis inhibitors granulocyte colony-stimulating factor (G-CSF) and granulocyte/macrophage colony-stimulating factor (GM-CSF) before and after the onset of ARDS; and to determine whether the BALF concentrations of G-CSF and/or GM-CSF are associated with clinical outcome. DESIGN: Prospective cohort study. SETTING: Tertiary university hospital. PATIENTS: Twenty patients at risk for ARDS and 45 patients with established ARDS. INTERVENTIONS: Patients at risk for ARDS underwent bronchoalveolar lavage within 24 hrs of being identified, then again 72 hrs later. Patients with ARDS underwent bronchoalveolar lavage within 24 hrs of meeting ARDS criteria, then again on days 3, 7, and 14 of the disease. MEASUREMENTS AND MAIN RESULTS: Normal peripheral blood neutrophil were incubated overnight in BALF from normal volunteers, from patients at risk for ARDS, or from patients with ARDS. neutrophil apoptosis was determined by flow cytometric analysis of annexin V binding. G-CSF and GM-CSF were measured in BALF by immunoassays. Compared with normal BALF, BALF from patients on days 1 and 3 of ARDS inhibited neutrophil apoptosis, but BALF from patients at later stages of ARDS, or from patients at risk for ARDS, did not. The BALF concentrations of both G-CSF and GM-CSF were elevated early in ARDS and decreased toward later stages. Patients who lived had significantly higher concentrations of GM-CSF in the BALF than those who died. CONCLUSIONS: We conclude that the antiapoptotic effect of ARDS BALF on normal neutrophil is highest during early ARDS, and decreases during late ARDS. G-CSF and GM-CSF are present in BALF from patients with ARDS, and their concentrations parallel the antiapoptotic effect of ARDS BALF. These data support the concept that the life-span of neutrophil in the air spaces is modulated during acute inflammation. GM-CSF in the air spaces is associated with improved survival in patients with ARDS.