title: Lithium attenuates lipopolysaccharide-induced hypothermia in rats.
abstract: BACKGROUND
  Changes in body temperature are common features among patients with sepsis and septic shock. Similarly, systemic administration of bacterial endotoxin (lipopolysaccharide, LPS) to rats leads to an initial hypothermia followed by elevation in body temperature. These changes in body temperature are accompanied by increased levels of prostaglandin E2 (PGE2) in the hypothalamus.
  
  
  OBJECTIVE
  This study examined the effects of lithium and SB216763 - two different glycogen synthase kinase (GSK)-3 inhibitors - on LPS-induced changes in body temperature and hypothalamic PGE2 levels in endotoxemic rats.
  
  
  METHODS
  Endotoxemia was induced by intraperitoneal injection of LPS (10 mg/kg). Lithium (100 mg/kg) and SB216763 (5 mg/kg) were administered at 2 h before LPS. Body temperature and mortality were monitored during 48 h after LPS injection. In another protocol, rats were sacrificed at 2 h post LPS injection and then, blood, liver and hypothalamus were extracted for inflammatory mediators determination.
  
  
  RESULTS
  Lithium but not SB216763 significantly reduced LPS-induced hypothermia, while both compounds did not alter the subsequent elevation in body temperature. Moreover, only lithium significantly reduced hypothalamic PGE2 levels. On the other hand, both compounds significantly reduced plasma, hepatic and hypothalamic tumor necrosis factor-α and decreased plasma PGE2 levels. Both compounds did not alter LPS-induced mortality.
  
  
  CONCLUSIONS
  These results suggest that the attenuation of LPS-induced hypothermia by lithium may derive from its reduction of hypothalamic PGE2 levels.
authors.affiliation: Department of Clinical Biochemistry and Pharmacology; Department of Cardiology, Soroka University Medical Center; Department of Nursing, School for Community Health Professions - Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel. azab@bgu.ac.il.
authors.forename: J
authors.initials: J
authors.lastname: Kaplanski
authors.forename: A
authors.initials: A
authors.lastname: Nassar
authors.forename: Y
authors.initials: Y
authors.lastname: Sharon-Granit
authors.forename: A
authors.initials: A
authors.lastname: Jabareen
authors.forename: S L
authors.initials: SL
authors.lastname: Kobal
authors.forename: A N
authors.initials: AN
authors.lastname: Azab
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001831:Body Temperature / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism; D019446:Endotoxemia / Q000139:chemically induced / Q000188:drug therapy*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007035:Hypothermia / Q000139:chemically induced / Q000188:drug therapy*; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D008070:Lipopolysaccharides; D018021:Lithium Chloride / Q000494:pharmacology / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008301:Maleimides / Q000494:pharmacology / Q000627:therapeutic use; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D007211:Indoles; D008070:Lipopolysaccharides; D008301:Maleimides; C417521:SB 216763; D014409:Tumor Necrosis Factor-alpha; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride; D015232:Dinoprostone