• M E Astiz, E C Rackow, Y B Kim, and M H Weil.
• Department of Medicine, University of Health Sciences, Chicago Medical School, Illinois.
• Circ. Shock. 1991 Feb 1;33(2):92-7.

AbstractMonophosphoryl 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.

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