Systemic inflammatory priming in normal pregnancy and preeclampsia: the role of circulating syncytiotrophoblast microparticles.
Systemic inflammatory responsiveness was studied in normal human pregnancy and its specific inflammatory disorder, pre-eclampsia. Compared with nonpregnancy, monocytes were primed to produce more TNF-alpha throughout normal pregnancy, more IL-12p70 in the first and second trimesters, and more IL-18 in the first trimester only. Intracellular cytokine measurements (TNF-alpha and IL12p70) showed little change by comparison. IFN-gamma production was suppressed in all three trimesters. In pre-eclampsia, IL-18 secretion was increased. Secreted but not intracellular measures of TNF-alpha and IL-12p70 were also further enhanced compared with normal pregnancy. Inhibition of IFN-gamma production was lost and involved both CD56(+) NK and CD56(-) lymphocyte subsets. We determined whether circulating syncytiotrophoblast microparticles (STBM) could contribute to these inflammatory changes. Unbound STBM could be detected in normal pregnancy by the second trimester and increased significantly in the third. They were also bound in vivo to circulating monocytes. Women with pre-eclampsia had significantly more circulating free but not cell-bound STBMs. STBMs prepared by perfusion of normal placental lobules stimulated production of inflammatory cytokines (TNF-alpha, IL12p70, and IL-18 but not IFN-gamma) when cultured with PBMCs from healthy nonpregnant women. Inflammatory priming of PBMCs during pregnancy is confirmed and is established by the first trimester. It is associated with early inhibition of IFN-gamma production. The inflammatory response is enhanced in pre-eclampsia with loss of the IFN-gamma suppression. Circulating STBMs bind to monocytes and stimulate the production of inflammatory cytokines. It is concluded that they are potential contributors to altered systemic inflammatory responsiveness in pregnancy and pre-eclampsia.
Germain
Sarah J
SJ
Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
Sacks
Gavin P
GP
Sooranna
Suren R
SR
Soorana
Suren R
SR
Sargent
Ian L
IL
Redman
Christopher W
CW
D000328:Adult; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D011225:Pre-Eclampsia / Q000276:immunology*; D011247:Pregnancy; D014327:Trophoblasts / Q000276:immunology*
D016207:Cytokines; D007371:Interferon-gamma