Monophosphoryl lipid A induces tolerance to the lethal hemodynamic effects of endotoxemia.
Monophosphoryl lipid A (MPL) is a nontoxic derivative of lipid A. In this study, the induction of tolerance by MPL to the hemodynamic effects of lethal endotoxemia was tested. Ten Sprague-Dawley rats were received either Salmonella minnesota MPL 0.5 mg/100 g intravenously (i.v.) or equivalent volume of diluent (control) i.v. on day zero. On day 3 S. minnesota endotoxin (LPS) 5.0 mg/100 g was administered i.v. Cardiac output (CO), arterial lactate (L), and central venous oxygen saturation (SvO2) were measured before and 3 and 6 hr after LPS administration. Survival was determined at 72 hr. At 6 hr, CO was 217 +/- 11 ml/kg/min in controls, and 435 +/- 28 ml/kg/min in the MPL animals (P less than 0.01). Arterial lactate was 2.6 +/- 0.3 mmol/liter in controls and 1.3 +/- 0.2 mmol/liter in MPL animals at 6 hr (P less than 0.05). The controls died 7.5 +/- 1.3 hr after LPS administration, whereas all the MPL-pretreated animals survived. These data indicate that MPL induces tolerance to the acute hemodynamic effects of LPS and enhances survival from lethal endotoxemia.
Astiz
M E
ME
Department of Medicine, University of Health Sciences, Chicago Medical School, Illinois.
Rackow
E C
EC
Kim
Y B
YB
Weil
M H
MH
D000818:Animals; D002302:Cardiac Output; D006439:Hemodynamics; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D008070:Lipopolysaccharides; D010100:Oxygen / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D012475:Salmonella; D012772:Shock, Septic / Q000139:chemically induced / Q000503:physiopathology*
D007773:Lactates; D008050:Lipid A; D008070:Lipopolysaccharides; D019344:Lactic Acid; C048436:monophosphoryl lipid A; D010100:Oxygen