Mortality due to gram-negative septic shock remains high despite advances i
n medical care. Induction of endotoxin tolerance might be a new treatment s
trategy to prevent septic shock in the newborn. The present study was perfo
rmed to show that an injection in pregnant rats of monophosphoryl lipid A (
MPL), a nontoxic derivative of lipopolysaccharide (LPS), induces tolerance
to Salmonella enteritidis LPS and tumor necrosis factor alpha (TNF-alpha) i
n their offspring. MPL at a dose of 2 mg/kg was injected into pregnant rats
on the 19th day of gestation. Their 0-day-old offspring later received an
intraperitoneal injection of S. enterifidis LPS or TNF-alpha. Newborn rats
of MPL-treated dams exhibited a higher survival rate, absence of lactacidem
ia and lower plasma TNF-alpha concentration in response to S.enteritidis LP
S when compared to the newborn rats of saline-treated darns. Newborn rats o
f MPL-treated darns were more tolerant to TNF-alpha than those of saline-tr
eated darns. MPL injection into pregnant rats did not increase plasma endot
oxin concentration in the fetuses, suggesting no placental passage rook pla
ce, but it did increase plasma TNF-alpha concentration. We concluded that a
n injection of MPL into pregnant rats induced tolerance to LPS in their off
spring, which might be due to TNF-alpha-induced TNF-alpha tolerance. Copyri
ght (C) 2000 S. Karger AG, Basel.