Lithium attenuates lipopolysaccharide-induced hypothermia in rats

J. Kaplanski, A. Nassar, Y. Sharon-Granit, A. Jabareen, S. L. Kobal, A. N. Azab

Research output: Contribution to journalReview articlepeer-review

15 Scopus citations


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. MATERIALS AND 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-a 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.

Original languageEnglish
Pages (from-to)1829-1837
Number of pages9
JournalEuropean Review for Medical and Pharmacological Sciences
Issue number12
StatePublished - 1 Jan 2014


  • Cytokines
  • Inflammation
  • Lithium
  • SB216763
  • Sepsis

ASJC Scopus subject areas

  • Pharmacology (medical)


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