THE ASSOCIATION BETWEEN MORTALITY-RATES AND DECREASED CONCENTRATIONS OF INTERLEUKIN-10 AND INTERLEUKIN-1 RECEPTOR ANTAGONIST IN THE LUNG FLUIDS OF PATIENTS WITH THE ADULT-RESPIRATORY-DISTRESS-SYNDROME

Objectives: To determine the relation between 1) intraalveolar concent rations of the proinflammatory cytokines (tumor necrosis factor, inter leukin-1 beta, and interleukin-8) and the anti-inflammatory cytokines (interleukin-10 and interleukin-1 receptor antagonist) in patients wit h early adult respiratory distress syndrome (ARDS) and 2) subsequent p atient mortality rates. Design: Prospective cohort study. Setting: Uni versity medical center. Patients: 28 consecutive patients in whom ARDS was prospectively identified during hospitalization and 9 ventilated controls. Measurements: Concentrations of proinflammatory cytokines an d anti-inflammatory cytokines in bronchoalveolar lavage fluid. Results : The concentrations of proinflammatory and anti-inflammatory cytokine s within the alveolar air spaces were significantly elevated in patien ts with ARDS compared with controls (P = 0.01 for tumor necrosis facto r [median, 90 pg/mL (range, 0 to 2500 pg/mL) for patients with ARDS; m edian, 0 pg/mL (range, 0 to 118 pg/mL) for controls]; P = 0.001 for in terleukin-1 beta [median, 179 pg/mL (range, 0 to 2200 pg/mL) for patie nts with ARDS; median, 0 pg/mL (range, 0 to 80 pg/mL) for controls]; P = 0.0001 for interleukin-8 [median, 628 pg/mL (range, 0 to 4700 pg/mL ) for patients with ARDS; median, 0 pg/mL (range, 0 to 278 pg/mL) for controls]; P = 0.0005 for interleukin-10 [median, 100 pg/mL (range, 0 to 1600 pg/mL) for patients with ARDS; median, 0 pg/mL (range, 0 to 50 pg/mL) for controls], and P = 0.002 for interleukin-1 receptor antago nist [median, 820 pg/mL (range, 0 to 18 900 pg/mL) for patients with A RDS; median, 50 pg/mL (range, 0 to 240 pg/mL) for controls]). A highly significant correlation was found between low concentrations of anti- inflammatory cytokines and subsequent patient mortality rates (P = 0.0 03 for interleukin-10 [median, 120 pg/mL (range, 30 to 1600 pg/mL) for survivors; median, 40 pg/mL (range, 0 to 110 pg/mL) for nonsurvivors] ; P = 0.008 for interleukin-1 receptor antagonist [median, 1600 pg/mL (range, 80 to 18 900 pg/mL) for survivors; median, 90 pg/mL (range, 0 to 3400 pg/mL) for nonsurvivors. No significant correlation was found between the concentrations of the proinflammatory cytokines and mortal ity rates. Conclusion: Low concentrations of the anti-inflammatory cyt okines interleukin-10 and interleukin-1 receptor antagonist in broncho alveolar lavage fluid obtained from patients with early ARDS are close ly associated with poor prognosis. These findings support the hypothes is that failure to mount a localized intrapulmonary anti-inflammatory response early in the pathogenesis of ARDS contributes to more severe organ injury and worse prognosis. Our findings suggest that augmenting anti-inflammatory cytokine defenses would be a beneficial therapeutic approach to patients with ARDS and other inflammatory diseases.