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1 August 1996 | Volume 125 Issue 3 | Pages 191-196
Objectives: To determine the relation between 1) intraalveolar concentrations of the proinflammatory cytokines (tumor necrosis factor, interleukin-1 ß, and interleukin-8) and the anti-inflammatory cytokines (interleukin-10 and interleukin-1 receptor antagonist) in patients with early adult respiratory distress syndrome [ARDS] and 2) subsequent patient mortality rates.
Design: Prospective cohort study.
Setting: University medical center.
Patients: 28 consecutive patients in whom ARDS was prospectively identified during hospitalization and 9 ventilated controls.
Measurements: Concentrations of proinflammatory cytokines and anti-inflammatory cytokines in bronchoalveolar lavage fluid.
Results: The concentrations of proinflammatory and anti-inflammatory cytokines within the alveolar air spaces were significantly elevated in patients with ARDS compared with controls (P = 0.01 for tumor necrosis factor [median, 90 pg/mL (range, 0 to 2500 pg/mL) for patients with ARDS; median, 0 pg/mL (range, 0 to 118 pg/mL) for controls]; P = 0.001 for interleukin-1 ß [median, 179 pg/mL (range, 0 to 2200 pg/mL) for patients 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 antagonist [median, 820 pg/mL (range, 0 to 18 900 pg/mL) for patients with ARDS; 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 = 0.003 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 mortality rates.
Conclusion: Low concentrations of the anti-inflammatory cytokines interleukin-10 and interleukin-1 receptor antagonist in bronchoalveolar lavage fluid obtained from patients with early ARDS are closely associated with poor prognosis. These findings support the hypothesis 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.
Author and Article Information
From the University of Edinburgh, the Royal Infirmary, and Western General Hospitals, Edinburgh, United Kingdom, and University of Michigan, Ann Arbor, Michigan.
ARTICLE
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
Acknowledgments: The authors thank the staff of the intensive therapy units at the Royal Infirmary and Western General Hospitals, Edinburgh, United Kingdom, for their help and cooperation.
Grant Support: In part by the British Lung Foundation and Chest, Heart, and Stroke Scotland.
Requests for Reprints: Christopher Haslett, FRCP, Rayne Laboratory, University Medical School, Teviot Place, Edinburgh, EH8 9AG, Scotland.
Current Author Addresses: Drs. Donnelly and Reid and Professor Haslett: Respiratory Medicine Unit, University of Edinburgh, Edinburgh, Scotland.
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