SUBLETHAL DOSE OF LPS TO PREGNANT RATS INDUCES TNF-ALPHA TOLERANCE INTHEIR 0-DAY-OLD OFFSPRING

The newborn has high mortality in septic shock. Induction of endotoxin tolerance may prevent endotoxic shack in the newborn. The present stu dy showed that a small dose of Salmonella enteritidis Lipopolysacchari de (S. ent. LPS): Rc mutant Escherichia coli lipopolysaccharide (J5 LP S), or tumor necrosis factor-alpha (TNF-alpha) given to pregnant rats on the 19th day of gestation induced endotoxin tolerance in their 0-da y-old offspring. S. ent. LPS or J5 LPS injected into pregnant rats inc reased plasma endotoxin-like activity in dams, although not in their f etuses, and increased plasma TNF-alpha concentration in both dams and their fetuses. The endotoxin-tolerant newborn rats were also resistant to TNF-alpha. In those newborn rats, an LPS injection increased plasm a TNF-alpha concentration and liver TNF-alpha mRNA abundance. These ex periments showed that the endotoxin tolerance could be due to TNF-alph a tolerance. In conclusion, prenatal treatment of dams with a small do se of S. ent. LPS, J5 LPS, or TNF-alpha was beneficial in preventing e ndotoxic shock in the newborn.