Cytokine secretion by decidual lymphocytes in transient hypertension of pregnancy and pre‐eclampsia

Abstract

BACKGROUND: Transient hypertension (TH) and preeclampsia (PE) are believed to have different pathophysiology. However, 15-25% of pregnant women initially diagnosed as having TH develop PE. To clarify the immuno-pathogenetical connections between the two syndromes, we studied the pattern of T helper cell (Th)1/Th2 cytokine balance disturbances existing inside maternal decidua in normal pregnancy (NP) and pregnancies complicated with TH and PE. METHODS: Third-trimester decidual tissue was obtained by curettage of uterine cavity during elective caesarean sections in NP (n = 11), TH (n = 17) and PE (n = 21) patients. Cell suspensions were prepared by an electromechanical dispersal method and centrifugated using a standard gradient sedimentation technique. Isolated lymphocytes were placed in medium (RPMI 1640, 10% fetal calf serum, L-glutamine, penicillin, streptomycin) and cultured for 72 h with or without mitogen phytohaemaglutinine (PHA). The enzyme-linked immunosorbent assay method was used for estimation of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12 and interferon-gamma (IFN-gamma) in culture supernatant. STATISTICAL ANALYSIS: The Kruskal-Wallis and the Mann-Whitney U tests were used (p < 0.05). RESULTS: Both spontaneous and PHA-stimulated secretion of Th2-type cytokines IL-6 and IL-10 was decreased in PE patients compared with TH and NP patients. The concentration of Th1-type cytokine IFN-gamma was increased in patients suffering both from TH and PE. CONCLUSION: On the base of decidual cytokine secretion, both PE and TH are syndromes of local Th1/Th2 cytokine balance disturbances as compared with NP, and TH seems to be an intermediate step to PE.

Immunological Analogy Between Allograft Rejection, Recurrent Abortion and Pre-Eclampsia – the Same Basic Mechanism?

“…However, as was shown, RA pregnancies were characterized by low protection which resulted from down-regulated HLA-G molecule [221] and increased expression of classical HLA antigens [217]. Similarly, in PE pregnancies, down-regulation of HLA-G was accompanied by a progressive increase in classical HLA that resulted both from natural trophoblast aging and increased levels of IFN␥ secreted by decidual immunocytes [203,218,219,252]. The sparse presence of anti-HLA antibodies in RA patients resulted probably from the failure to carry gestation long enough to produce response [7].…”

“…Activated decidual macrophages were also suspected of secreting IL-12, which subsequently increased IFN␥ and IL-2 production by decidual NK and T cells [201,202]. Exceptionally high secretion of IFN␥ with simultaneous low production of IL-10 was found in cultures of mitogen stimulated 3 rd trimester decidual lymphocytes of PE patients [203]. However, some investigators showed that both excessive Th1 and Th2 cytokine serum concentrations were correlated with symptoms of pre-eclampsia [204,205].…”

Hypoxia-inducible Factor 1 Transactivates the Human Leptin Gene Promoter

“…It would be of interest to know whether these factors could regulate leptin gene expression in some cell types by activating hypoxia-independent HIF-1 pathways. Interestingly, this could be the case in the hypoxic placenta during preeclampsia, in which increased inflammatory cytokine production has been described (29,30).…”

Expression Profile of C19MC microRNAs in Placental Tissue in Pregnancy-Related Complications

“…Interleukin 6 receptor Placentas of preeclamptic patients produce less sIL6R, but more gp130 (IL-6 receptor subunit beta) than placentas of normal pregnant patients (Wilczyński et al, 2002).…”