AJP - Regulatory, Integrative and Comparative Physiology, Vol 273, Issue 3 1158-R1162, Copyright © 1997 by American Physiological Society
A sublethal dose of LPS to pregnant rats induces TNF-alpha tolerance in their 0-day-old offspring
M. Goto, T. Yoshioka, R. I. Young, T. Battelino, C. L. Anderson and W. P. Zeller
Ronald McDonald Children's Hospital at Loyola, Maywood, Illinois, USA.
The newborn has high mortality in septic shock. Induction of endotoxin
tolerance may prevent endotoxic shock in the newborn. The present study
showed that a small dose of Salmonella enteritidis lipopolysaccharide (S.
ent. LPS), Rc mutant Escherichia coli lipopolysaccharide (J5 LPS), or tumor
necrosis factor-alpha (TNF-alpha) given to pregnant rats on the 19th day of
gestation induced endotoxin tolerance in their 0-day-old offspring. S. ent.
LPS or J5 LPS injected into pregnant rats increased plasma endotoxin-like
activity in dams, although not in their fetuses, 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 plasma TNF-alpha concentration and
liver TNF-alpha mRNA abundance. These experiments showed that the endotoxin
tolerance could be due to TNF-alpha tolerance. In conclusion, prenatal
treatment of dams with a small dose of S. ent. LPS, J5 LPS, or TNF-alpha
was beneficial in preventing endotoxic shock in the newborn.
