Hypothermia induces interleukin-10 and attenuates injury in the lungs of endotoxemic rats

Shock. 2003 Jul;20(1):41-5. doi: 10.1097/01.shk.0000071080.50028.f2.

Abstract

We recently reported that hypothermia protects against intrapulmonary nitric oxide overproduction and nitric oxide-mediated lung injury in endotoxemic rats. Few studies have been performed to investigate whether hypothermia reduces inflammation by affecting favorable changes in chemokine and pro- and anti-inflammatory cytokine profiles. In this study, we tested the hypothesis that hypothermia decreases concentrations of growth-related oncogene/cytokine-induced neutrophil chemoattractant-1 (GRO/CINC-1), interleukin (IL)-1beta, IL-6, and myeloperoxidase and increases concentration of IL-10 in the lungs endotoxemic rats. Twelve rats were anesthetized and randomized to treatment with either hypothermia (T = 18-24 degrees C; n = 6) or normothermia (T = 36-38 degrees C, n = 6). Endotoxin (15 mg/kg of Escherichia coli lipopolysaccharide) was administered intravascularly and lung tissue was harvested 150 min later. Three additional rats were sham instrumented and maintained as normothermic but not given endotoxin. Hematoxylin & eosin staining was performed for qualitative inspection of tissues. Quantitative analyses of lung homogenates were performed using enzyme-linked immunosorbent assays for IL-1beta, IL-6, IL-10, and GRO/CINC-1. Myeloperoxidase concentrations were determined using a colorimetric assay. Hypothermia attenuated the induction of intrapulmonary IL-1beta (P < 0.05), IL-6 (P < 0.05), GRO/CINC-1 (P < 0.05), and myeloperoxidase (P < 0.05) caused by endotoxin. Inspection of the lungs revealed that hypothermia similarly attenuated histological signs of injury, such as interstitial edema and neutrophil accumulation. Hypothermia increased the intrapulmonary concentration of IL-10 more than 3-fold over that measured in the normothermia (endotoxin-exposed) group (P < 0.05). Hypothermia inhibits neutrophil recruitment in the lungs of endotoxemic rats in part by decreasing proinflammatory cytokine expression. Additionally, hypothermia induces intrapulmonary IL-10 expression. Further studies are needed to investigate whether IL-10 mediates the anti-inflammatory effects of hypothermia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Pressure
  • Chemokine CXCL1
  • Chemokines / metabolism
  • Chemokines, CXC*
  • Chemotactic Factors / metabolism
  • Disease Models, Animal
  • Endotoxemia / metabolism
  • Endotoxemia / physiopathology*
  • Endotoxemia / therapy*
  • Heart Rate
  • Hypothermia, Induced* / adverse effects
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Interleukin-1 / metabolism
  • Interleukin-10 / metabolism*
  • Interleukin-6 / metabolism
  • Lung / metabolism
  • Lung / pathology*
  • Lung Injury
  • Male
  • Peroxidase / metabolism
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Chemokine CXCL1
  • Chemokines
  • Chemokines, CXC
  • Chemotactic Factors
  • Cxcl1 protein, rat
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-1
  • Interleukin-6
  • Interleukin-10
  • Peroxidase