title: Hypothermia induces anti-inflammatory cytokines and inhibits nitric oxide and myeloperoxidase-mediated damage in the hearts of endotoxemic rats.
abstract: OBJECTIVE
  s: The impairment of cardiac contractility during endotoxemia involves induction of nitric oxide formation through a cascade of events initiated by overexpression of proinflammatory cytokines. We previously showed that hypothermia attenuates endotoxin-induced overexpression of nitric oxide in rat lungs. In the present study, we tested the hypothesis that hypothermia protects against endotoxin-induced myocardial inflammation by changing the balance of pro- and anti-inflammatory cytokines, inhibiting myeloperoxidase, an indicator of neutrophil activity, and inhibiting nitric oxide-mediated protein damage.
  
  
  METHODS
  Rats were randomized to treatment with either hypothermia (n = 6; 18 to 24 degrees C) or normothermia (n = 6; 36 to 38 degrees C). Endotoxin (15 mg/kg) was administered intravascularly to anesthetized animals, and heart tissue was harvested 150 min later.
  
  
  RESULTS
  Using enzyme-linked immunosorbent assays (ELISAs), we found that hypothermia induced myocardial expression of the anti-inflammatory cytokines interleukin (IL)-4 and IL-10, while decreasing concentrations of the pro-inflammatory cytokines IL-1beta and growth-related oncogene/cytokine-induced neutrophil chemoattractant (rat homolog of IL-8). Electromobility shift assay revealed that hypothermia inhibited the nuclear translocation of nuclear factor-kappaB. Reverse transcriptase-polymerase chain reaction and Western blot assays revealed that hypothermia attenuated the endotoxin-induced overexpression of both inducible nitric oxide synthase (iNOS) messenger RNA and iNOS protein, respectively. Hypothermia also attenuated nitric oxide-mediated myocardial protein damage, as determined by a nitrotyrosine ELISA. Myocardial myeloperoxidase content, an indicator of neutrophil accumulation and oxidative activity, was also inhibited by hypothermia in endotoxemic rats.
  
  
  CONCLUSIONS
  These data demonstrate that hypothermia induces an anti-inflammatory cytokine profile, inhibits neutrophil aggregation, and inhibits the formation of nitric oxide during endotoxemia in the rat.
authors.affiliation: Department of Pediatrics, University of Florida, Gainesville, USA.
authors.forename: Philip O
authors.initials: PO
authors.lastname: Scumpia
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Sarcia
authors.forename: Kindra M
authors.initials: KM
authors.lastname: Kelly
authors.forename: Vincent G
authors.initials: VG
authors.lastname: DeMarco
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Skimming
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D019446:Endotoxemia / Q000378:metabolism* / Q000628:therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D007036:Hypothermia, Induced; D007249:Inflammation / Q000517:prevention & control; D007375:Interleukin-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009195:Peroxidase / Q000037:antagonists & inhibitors*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D016209:Interleukin-8; D016328:NF-kappa B; D016753:Interleukin-10; D015847:Interleukin-4; D009569:Nitric Oxide; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat