title: Hypothermia induces interleukin-10 and attenuates injury in the lungs of endotoxemic rats.
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.
authors.affiliation: Department of Pediatrics, University of Florida, Gainesville, Florida, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Sarcia
authors.forename: Philip O
authors.initials: PO
authors.lastname: Scumpia
authors.forename: Lyle L
authors.initials: LL
authors.lastname: Moldawer
authors.forename: Vincent G
authors.initials: VG
authors.lastname: DeMarco
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Skimming
mesh_terms: D000818:Animals; D001794:Blood Pressure; D054360:Chemokine CXCL1; D018925:Chemokines / Q000378:metabolism; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000378:metabolism; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy*; D006339:Heart Rate; D007036:Hypothermia, Induced / Q000009:adverse effects; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D055370:Lung Injury; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C513297:Cxcl1 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D016753:Interleukin-10; D009195:Peroxidase