Lithium attenuates lipopolysaccharide-induced hypothermia in rats

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.