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Rebound Inflammation Associated with Rewarming from Hypothermia in an Endotoxin-Injured Lung
임채만 대한중환자의학회 2013 Acute and Critical Care Vol.28 No.2
Background: Hypothermia is known to suppress inflammation in various experimental and clinical settings. We wanted to investigate how the suppressed inflammation by hypothermia is affected during rewarming. Methods: Mice were being assigned to normothermia (37oC) or hypothermia (32oC). After 30 minutes at the assigned temperature, lipopolysaccharide was administered intratracheally. The mice were then randomly grouped and subjected to 4 hours of normothermia (N), 24 hours of normothermia (NN), 4 hours of hypothermia (H), or 4 hours of hypothermia followed by normothermia for the next 20 hours (HN). In another experiment, other HN mice were treated with varying doses of anti-TNF-α or anti-IL-1β antibodies (0, 6.25, 12.5, 25, and 50 μg/250 μl) immediately prior to rewarming. Results: The neutrophil counts of BAL fluid (×104/ml) were 23.0 ± 13.1 in the N, 6.4 ± 3.1 in the H (p = 0.002 vs N), 20.4 ± 10.2 in the NN, and 49.7 ± 21.0 in the HN (p = 0.005 vs H; p < 0.001 vs NN). Myeloperoxidase activity of the lung (unit/μg) was 6.7 ± 2.9, 7.9 ± 1.9, 17.8 ± 4.0 (p < 0.001 vs N), and 12.9 ± 5.9 (p = 0.034 vs H, p = 0.028 vs NN), respectively. Compared with control HN, total WBC and neutrophil counts of mice treated with anti-TNF-α antibody or anti-IL-1β antibody prior to rewarming were lower at all tested doses. The combination of both anti-TNF-α or anti-IL-1β antibodies was not increasingly reducing the neutrophilic sequestration. Conclusions: Rewarming from induced hypothermia resulted in augmentation of neutrophilic sequestration of endotoxin-injured lung. Treatment with antibodies against TNF-α or IL-1β prevented this rebound of neutrophilic infiltration.