Hypothermia protects against endotoxin-induced acute lung injury in rats

Intensive Care Med. 2003 Mar;29(3):453-9. doi: 10.1007/s00134-002-1529-6. Epub 2002 Nov 22.


Objective: Hypothermia in humans and animals is known to decrease the number and function of circulating neutrophils. Because an activation of circulating neutrophils and their sequestration into the lung are important pathogenetic phenomena in endotoxin-associated lung injury, we conjectured that hypothermia could prevent this type of lung injury.

Design and setting: Animal study at a university-affiliated research institute.

Subjects: Thirty-six Sprague-Dawley rats.

Interventions: After anesthesia, the rats were randomly assigned to normothermia (37 degrees C, rectal temperature) or hypothermia (27 degrees C), which was induced by surface cooling. After 1 h of stable temperature, the rats were administered intratracheal doses of lipopolysaccharide (LPS; 3 mg/kg) (normothermia-LPS; hypothermia-LPS) or an equivalent volume of normal saline (normothermia-saline; hypothermia-saline). The rectal temperature was maintained within +/-1 degrees C of the target temperature for 6 h after the intratracheal treatment.

Measurements and results: Compared with the normothermia-LPS group, the neutrophil count in bronchoalveolar lavage (BAL) fluid (p=0.002) and the myeloperoxidase activity of lung tissues (p=0.002) of the hypothermia-LPS group were both lower. Compared with the normothermia-LPS group, the BAL interleukin-1beta level of the hypothermia-LPS group was lower (p<0.001), whereas the BAL interleukin-10 level of the hypothermia-LPS group was higher (p=0.026). Compared with the normothermia-LPS group, the histologic scores for acute lung injury of the hypothermia-LPS group were lower (p=0.007).

Conclusions: Hypothermia pretreatment decreased the pulmonary sequestration of neutrophils, induced a favorable balance between pro- and anti-inflammatory cytokines, and attenuated histologic injury in endotoxin-challenged rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Bronchoalveolar Lavage Fluid / immunology
  • Cell Count
  • Hypothermia, Induced*
  • Interleukin-1 / biosynthesis
  • Interleukin-10 / biosynthesis
  • Lipopolysaccharides / toxicity
  • Lung / pathology*
  • Male
  • Neutrophils / immunology*
  • Peroxidase / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Statistics, Nonparametric
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Interleukin-1
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Peroxidase