Interleukin-2 involvement in early acute respiratory distress syndrome: relationship with polymorphonuclear neutrophil apoptosis and patient survival.
OBJECTIVE
To determine blood and lung alveolar concentrations of interleukin (IL)-2 in acute respiratory distress syndrome (ARDS) and their relationship with polymorphonuclear neutrophil (PMN) apoptosis and patient survival.


METHODS
Prospective cohort study.


METHODS
Medical and surgical intensive care units (ICUs; Canada) and the intensive care department (Belgium).


METHODS
Nineteen consecutive patients with ARDS, 14 non-ARDS ICU patients, and 20 healthy volunteers.


METHODS
Blood samples and bronchoalveolar lavages (BAL) obtained via venous puncture and by fiberoptic bronchoscopy in the first 72 hrs after the onset of ARDS.


RESULTS
One early point concentration of IL-2 was measured in both blood and BAL fluids of the three groups. In vivo alveolar PMN apoptotic index in BAL fluids and the influence of BAL fluid exposure on normal blood PMN spontaneous apoptosis in vitro were evaluated. Blood IL-2 was significantly lower in patients with ARDS compared with non-ARDS ICU patients and controls. In contrast, IL-2 in BAL fluids of patients with ARDS was dramatically elevated compared with non-ARDS ICU patients and controls. ARDS survivors exhibited lower early IL-2 blood levels than nonsurvivors and generally had a higher IL-2 lung content Lung alveolar PMN apoptosis in vivo was lower in patients with ARDS in comparison with controls. This apoptotic index was correlated with corresponding IL-2 alveolar levels in patients with ARDS. Exposure of normal blood PMN to BAL fluids from patients with ARDS delayed apoptosis in vitro. Immunodepletions of IL-2, granulocyte-macrophage colony stimulating factor, and a combination of both cytokines from BAL fluids of ARDS patients significantly restored PMN apoptosis. The recovery of PMN apoptosis was more effective when IL-2 was depleted in BAL fluids from ARDS survivors compared with nonsurvivors.


CONCLUSIONS
Opposite and disproportional concentrations of IL-2 are observed in blood and lung fluids of patients with early ARDS. IL-2 significantly contributes (with granulocyte-macrophage colony stimulating factor) to the inhibition of PMN apoptosis in BAL fluids of patients with ARDS. Early low blood IL-2 and high IL-2-driven inhibition of PMN apoptosis are beneficial to survivors. Thus, IL-2 is a new candidate for monitoring in early ARDS and an interesting indicator of prognosis.
Lesur
O
O
Medical and Surgical Intensive Care Units, Université de Sherbrooke, PQ, Canada.
Kokis
A
A
Hermans
C
C
Fülöp
T
T
Bernard
A
A
Lane
D
D
D018806:APACHE; D017209:Apoptosis / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D016022:Case-Control Studies; D016638:Critical Illness; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood / Q000172:deficiency / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000032:analysis / Q000097:blood* / Q000172:deficiency / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology*; D011379:Prognosis; D011446:Prospective Studies; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000209:etiology / Q000276:immunology* / Q000401:mortality; D016019:Survival Analysis; D013997:Time Factors
D015415:Biomarkers; D007376:Interleukin-2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor