Bacterial lipopolysaccharide-mediated murine fetal death: the role of interleukin-1.
OBJECTIVE
Our purpose was to determine whether interleukin-1 is an important mediator of lipopolysaccharide-induced fetal death and, if so, whether interleukin-1 causes fetal death by inducing prostanoid formation in gestational tissues.


METHODS
Pregnant C3H/HeN mice were administered lipopolysaccharide, interleukin-1alpha, interleukin-beta, or vehicle on days 11 to 13 of pregnancy. Mice were killed 72 hours later and the fetal status was determined. Some mice were pretreated with anti-interleukin-1-receptor antibodies or indomethacin. Decidual explants were established from treated mice, and supernatants were assayed for interleukin-1beta and prostaglandin E2.


RESULTS
Decidua taken from lipopolysaccharide-treated mice produced significantly increased amounts of interleukin-1beta, and pretreatment with anti-interleukin-1-receptor antibodies reduced the proportion of fetal deaths after lipopolysaccharide administration from 100% to 33%. The administration of interleukin-1alpha caused fetal death in a dose-dependent fashion, and decidua taken from interleukin-1-treated mice produced significantly increased amounts of prostaglandin E2. However, pretreatment with doses of indomethacin that abrogated decidual prostaglandin E2 production did not reduce the proportion of fetal death after interleukin-1alpha administration.


CONCLUSIONS
Interleukin-1 is an important mediator of lipopolysaccharide-induced fetal death and causes fetal death by prostaglandin-independent effects.
Silver
R M
RM
Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City 84132, USA.
Edwin
S S
SS
Umar
F
F
Dudley
D J
DJ
Branch
D W
DW
Mitchell
M D
MD
D000818:Animals; D000906:Antibodies; D015232:Dinoprostone / Q000096:biosynthesis*; D005260:Female; D005313:Fetal Death / Q000209:etiology*; D007213:Indomethacin / Q000008:administration & dosage; D007375:Interleukin-1 / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000009:adverse effects*; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D011247:Pregnancy; D017472:Receptors, Interleukin-1 / Q000276:immunology
D000906:Antibodies; D007375:Interleukin-1; D008070:Lipopolysaccharides; D017472:Receptors, Interleukin-1; D015232:Dinoprostone; D007213:Indomethacin