Interleukin-1beta and bacterial endotoxin change the metabolism of prostaglandins E2 and F2alpha in intact term fetal membranes.
There is strong evidence that prostaglandins E2 and F2alpha (PGE2 and PGF2alpha) are involved in the initiation and maintenance of human parturition and that their production can be stimulated by a number of cytokines and in infection-induced preterm labour by bacterial endotoxin. This study used an intact fetal membrane disk model to investigate the regulation of PGE2 and PGF2alpha metabolism by interleukin-1 beta (IL-1beta) and bacterial endotoxin [lipopolysaccharide (LPS)]. Fetal membrane explants were incubated with IL-1beta (0.1 or 1.0 ng/ml) or LPS (10 ng/ml) for 24 h. A mixture of 3H-prostaglandin (0.1 microCi) and unlabelled prostaglandin (1 microg) was then added at selected times after the addition of inflammatory mediators. The radiolabelled prostaglandins and their metabolites were then extracted from the culture medium and quantified by high-pressure liquid chromatography. Levels of prostaglandin metabolites were generally decreased following incubation with IL-1beta or LPS, which is consistent with a decrease in the activity of 15-hydroxyprostaglandin dehydrogenase (PGDH). It is concluded that IL-1beta and LPS moderately decrease the metabolism of prostaglandins, which may contribute to increasing the local levels of active prostaglandins induced by these stimuli.
Brown
N L
NL
Department of Obstetrics and Gynaecology, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
Alvi
S A
SA
Elder
M G
MG
Bennett
P R
PR
Sullivan
M H
MH
D000328:Adult; D018929:Cell Culture Techniques; D002851:Chromatography, High Pressure Liquid; D015237:Dinoprost / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D005321:Extraembryonic Membranes / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D011247:Pregnancy
D007375:Interleukin-1; D008070:Lipopolysaccharides; D015237:Dinoprost; D015232:Dinoprostone