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

Ann Intern Med. 1996 Aug 1;125(3):191-6. doi: 10.7326/0003-4819-125-3-199608010-00005.

Abstract

Objectives: To determine the relation between 1) intra-alveolar concentrations of the proinflammatory cytokines (tumor necrosis factor, interleukin-1 beta, 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 beta [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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bronchoalveolar Lavage Fluid / chemistry*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Interleukin-1 / metabolism
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Male
  • Middle Aged
  • Prospective Studies
  • Receptors, Interleukin / metabolism*
  • Receptors, Interleukin-1 / antagonists & inhibitors*
  • Receptors, Interleukin-10
  • Respiratory Distress Syndrome, Adult / metabolism*
  • Respiratory Distress Syndrome, Adult / mortality*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Interleukin-1
  • Interleukin-6
  • Interleukin-8
  • Receptors, Interleukin
  • Receptors, Interleukin-1
  • Receptors, Interleukin-10
  • Tumor Necrosis Factor-alpha