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G P Sacks

Publications and source records attributed to G P Sacks.

9 recordsLinked to original sources
PubMed2004

Maternal C-reactive protein levels are raised at 4 weeks gestation.

BACKGROUND: The aim of this study was to determine whether there is evidence of a systemic maternal inflammatory response in very early pregnancy. METHODS: Successive women receiving treatment by IVF or ICSI had serum C-reactive protein (CRP) levels measured on the day of their pregnancy blood test at 4 weeks gestation (14 days post-egg collection). Women with positive betaHCG levels had ongoing pregnancies confirmed by serial transvaginal ultrasound scans up to 8 weeks gestation. RESULTS: Pregnant women (n = 40) were significantly younger (mean age 34 years) than women who failed to become pregnant (n = 95, mean age 37 years, P < 0.001), received significantly lower treatment doses of recombinant FSH (2000 versus 2400 IU, P < 0.05) and had significantly more eggs collected (11 versus 8, P < 0.01). There were no significant differences in body mass index, parity, a history of smoking, endometriosis or polycystic ovaries, pre-treatment CRP levels and white cell counts, peak serum estradiol levels and numbers of embryos transferred. Pregnant women had significantly higher CRP levels (median 3.68 mg/l) than those who were not pregnant (median 1.495 mg/l, P < 0.0001), a difference that persisted after excluding potential confounding variables. Six pregnant women with ovarian hyperstimulation syndrome had higher CRP levels than those who did not (P < 0.01). CONCLUSIONS: This well-controlled study is the first to demonstrate that maternal CRP levels are raised as early as 4 weeks gestation and thus that the maternal inflammatory response is established during the earliest phases of implantation. It is hypothesized that an abnormal response (either exaggerated or absent) could cause some cases of miscarriage.

Adult↗
PubMed2003

Trophoblast deportation and the maternal inflammatory response in pre-eclampsia.

We have proposed that the maternal syndrome of pre-eclampsia is caused by a systemic inflammatory response involving both leucocytes and endothelium. This inflammatory response is present also in normal pregnancy, but in a milder form. The inflammatory stimulus is most likely to come from the placenta. Syncytiotrophoblast apoptotic debris, which is shed into the maternal circulation in normal pregnancy and in increased amounts in pre-eclampsia, may be the stimulus for this response. It may also contribute to the suppression of Th1 responses seen in pregnancy.

Endothelium, Vascular↗
PubMed2003

Monocytes are primed to produce the Th1 type cytokine IL-12 in normal human pregnancy: an intracellular flow cytometric analysis of peripheral blood mononuclear cells.

This paper considers both monocytes and peripheral blood lymphocytes as potential targets for maternal immunological modulation in pregnancy. Peripheral blood mononuclear cells (PBMCs) from non-pregnant and normal pregnant donors were stimulated in vitro, and cytokine production detected intracellularly by flow cytometry. It was found that monocyte production of TNF-alpha was unaltered in pregnancy, while production of IL-12 was significantly enhanced. In contrast, production of the Th1 type cytokine IFN-gamma was suppressed in the lymphocyte subsets: CD4+ T helper cells and CD56+ NK cells. Production of the Th2 type cytokine IL-4 in CD4+ cells was not significantly altered in pregnancy. These data suggest that the concept that pregnancy is a 'Th2 phenomenon' cannot be generalized to the function of all aspects of maternal cellular immunity as, paradoxically, circulating monocytes are 'primed' to produce the Th1 cytokine IL-12. Furthermore, these data support the hypothesis that components of maternal innate immunity are activated in normal pregnancy.

Adult↗
PubMed2001

Flow cytometric measurement of intracellular Th1 and Th2 cytokine production by human villous and extravillous cytotrophoblast.

A wide variety of cytokines are present at the maternal-fetal interface, but the extreme cellular complexity of the placenta has made it difficult to determine which cytokines are produced by which cells. Hence novel flow cytometric methods have been applied to determine intracellular cytokine production by specific cell-types in placental cell suspensions. Cell suspensions were prepared from first and third trimester chorionic villi and third trimester amniochorion by enzymatic digestion and Percoll density gradient centrifugation. After overnight incubation in the presence of monensin, cells were fixed, permeabilized and labelled with antibodies for villous cytotrophoblast (cytokeratin+, MHC class I-), extravillous cytotrophoblast (cytokeratin+, MHC class 1+) and leucocytes (CD45+). These cell types were further characterized by their expression of EGFR (proliferative cytotrophoblast) and c-erbB2 (invasive cytotrophoblast). Production of IL-4, IL-10, TNF-alpha, IFN-gamma and IL-12 was determined by simultaneous labelling with the appropriate monoclonal antibodies. Only IL-4 was detected consistently in all samples of cytotrophoblast. IL-10 was not detected but IL-10 mRNA was demonstrated in third trimester chorionic villus digests by RT-PCR. Although IL-4 secretion has not been demonstrated, these data suggest that, in vivo there may be a "Th2 type cytokine bias" orchestrated by the trophoblast. It is proposed that other cytokines (including IL-10 and TNF-alpha) are produced by decidual leukocytes, and not cytotrophoblast, at the maternal-fetal interface.

Cell Separation↗
PubMed1999

Preeclampsia: an excessive maternal inflammatory response to pregnancy.

The maternal syndrome of preeclampsia has previously been ascribed to generalized maternal endothelial cell dysfunction. In this review we suggest that the endothelial dysfunction is a part of a more generalized intravascular inflammatory reaction involving intravascular leukocytes as well as the clotting and complement systems. We provide evidence from our recent work and that of others that not only supports this proposal but indicates that such an inflammatory response is already well developed in normal pregnancy and that the differences between normal pregnancy and preeclampsia are less striking than those between the normal pregnant and nonpregnant states. From this we argue that preeclampsia arises when a universal maternal intravascular inflammatory response to pregnancy decompensates in particular cases, which may occur because either the stimulus or the maternal response is too strong. We conclude that there is no specific cause for the disorder, which can be better considered as the extreme end of the range of maternal adaptation to pregnancy. We propose that poor placentation is not the cause of preeclampsia but is a powerful predisposing factor. We predict that a single preeclampsia gene will not be found, nor will either a single specific predictive test or single preventive effective measure be devised. Aspects of the hypothesis are testable, and future work should allow its confirmation or refutation.

Endothelium, Vascular↗
PubMed1998

Normal pregnancy and preeclampsia both produce inflammatory changes in peripheral blood leukocytes akin to those of sepsis.

OBJECTIVE: Our aim was to seek evidence for circulating leukocyte activation in preeclampsia. STUDY DESIGN: Whole blood flow cytometric techniques were used to analyze surface markers of activation (CD11b, CD14, CD23, CD49d, CD62L, CD64, CD66b, HLA-DR) and intracellular reactive oxygen species. Samples were taken from 21 women with preeclampsia, 21 matched normal pregnant women, 21 healthy nonpregnant controls, and 6 nonpregnant patients with septicemia. Ten preeclamptic cases were followed up 6 weeks post partum. RESULTS: The leukocytes of healthy pregnant women differed substantially and significantly from those of nonpregnant women (increased CD11b, CD14, and CD64 and increased intracellular reactive oxygen species). In preeclampsia there was, in addition to these changes, reduced expression of L-selectin and further increases in intracellular reactive oxygen species. The changes found in normal pregnancy and preeclampsia were similar, but not identical, to those found in sepsis. CONCLUSIONS: Normal third-trimester pregnancy is characterized by remarkable activation of peripheral blood leukocytes, which is further increased in preeclampsia.

Adult↗