Effect of ethanol and sodium arsenite on HSP-72 formation and on survival in a murine endotoxin model.
Recently, investigators reported that prophylactic hyperthermia and induction of heat shock proteins (HSPs) decreased mortality from endotoxin. Although the mechanism by which hyperthermia protects is unknown, two possible etiologies are induction of HSPs and/or production of cytokines, interleukin-1 alpha (IL-1 alpha) or tumor necrosis factor-alpha (TNF-alpha). The purpose of this study was to determine if in vivo administration of sodium arsenite (NaAsO2) or ethanol, inducers of HSPs in isolated cells, induced HSP-72 production in lung, liver, kidney, and duodenum (organs known to induce HSP-72 by heat) and improved survival from endotoxin. Female ND4 mice were injected intraperitoneally with either NaAsO2 (5.25 mg/kg body weight) or ethanol (4.0 g/kg), immediately, 8 or 18 h prior to Escherichia coli endotoxin injection (20 mg/kg). Both compounds improved short-term (24 h) survival twofold (p < .01), but failed to improve long-term (7 days) survival. Simultaneous injection of ethanol with endotoxin improved both short-term survival twofold (p < .01), and long-term survival 5-fold (p < .001). Ethanol induced HSP-72 in kidney, 50% that of the standard (i.e., pooled livers isolated from heat-treated mice); NaAsO2 induced HSP-72 in kidney (approximately 50% of standard) and liver (approximately 21% of standard). Neither ethanol nor NaAsO2 alone increased circulating concentrations of IL-1 alpha or TNF-alpha. However, ethanol given concurrently with endotoxin produced a significant decrease in TNF-alpha compared to endotoxin alone (p < .01).(ABSTRACT TRUNCATED AT 250 WORDS)
Lappas
G D
GD
Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Karl
I E
IE
Hotchkiss
R S
RS
D000818:Animals; D018053:Arsenites / Q000494:pharmacology; D004195:Disease Models, Animal; D004731:Endotoxins / Q000008:administration & dosage; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D051379:Mice; D009928:Organ Specificity; D012769:Shock / Q000139:chemically induced / Q000378:metabolism* / Q000401:mortality; D017670:Sodium Compounds / Q000494:pharmacology; D015996:Survival Rate
D018053:Arsenites; D004731:Endotoxins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D017670:Sodium Compounds; D000431:Ethanol; C017947:sodium arsenite