Glucocorticoids inhibit placental cytokines from cultured normal and preeclamptic placental explants.
Glucocorticoids are used in pregnancy to enhance fetal lung maturity as well as to ameliorate antepartum and postpartum HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, but it is not clear if glucocorticoids can modulate placental cytokine production. The aim of this study is to examine the effect of glucocorticoids at equivalent doses used for fetal lung maturity on placental tissue production of cytokines (IL-10, IL-6 and TNF-alpha). Placental biopsies were taken from the decidual surface of term placentas of normal pregnancy (n = 5) and preeclampsia (n = 5). Villous explants were cultured with increasing concentrations of glucocorticoids (betamethasone and methyl-prednisolone, 0.0025 microM, 0.25 microM and 25 microM). The dose effect of glucocorticoids on cytokines (TNF-alpha, IL-6 and IL-10) production was examined using ELISA. There was a stepwise reduction of TNF-alpha (23.6-97.5% reduction) and IL-6 (13.7-71% reduction) with increasing doses of betamethasone and methyl-prednisolone from placentas of women with preeclampsia and normal pregnancy. However, IL-10 was not altered in conditioned medium by increasing doses of glucocorticoids. Our data suggest that the ratio of pro-inflammatory to anti-inflammatory cytokine (Th1/Th2) is potentially altered by exogenous glucocorticoids. These changes have a favourable effect on the ratio in preeclampsia with a reduction in the potentially vascular active pro-inflammatory cytokines but without altering or decreasing the necessary anti-inflammatory cytokine IL-10 production in placental tissue.
Xu
B
B
Vascular Immunology Research Laboratory, The Heart Research Institute, University of Sydney, Camperdown, NSW, Australia. bei_xu2001@yahoo.com
Makris
A
A
Thornton
C
C
Hennessy
A
A
D000328:Adult; D001623:Betamethasone / Q000494:pharmacology*; D002824:Chorionic Villi / Q000187:drug effects* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005865:Gestational Age; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008775:Methylprednisolone / Q000494:pharmacology*; D009924:Organ Culture Techniques; D011225:Pre-Eclampsia; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D005938:Glucocorticoids; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011257:Pregnancy Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D001623:Betamethasone; D008775:Methylprednisolone