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.
OBJECTIVE
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.


METHODS
Prospective cohort study.


METHODS
University medical center.


METHODS
28 consecutive patients in whom ARDS was prospectively identified during hospitalization and 9 ventilated controls.


METHODS
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.


CONCLUSIONS
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.
Donnelly
S C
SC
University of Edinburgh, Royal Infirmary, United Kingdom.
Strieter
R M
RM
Reid
P T
PT
Kunkel
S L
SL
Burdick
M D
MD
Armstrong
I
I
Mackenzie
A
A
Haslett
C
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018123:Receptors, Interleukin / Q000378:metabolism*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D053701:Receptors, Interleukin-10; D012128:Respiratory Distress Syndrome / Q000378:metabolism* / Q000401:mortality*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D018123:Receptors, Interleukin; D017472:Receptors, Interleukin-1; D053701:Receptors, Interleukin-10; D014409:Tumor Necrosis Factor-alpha