The ratio of interleukin (IL)-18 to IL-12 secreted by peripheral blood mononuclear cells is increased in normal pregnant subjects and decreased in pre-eclamptic patients.
ABSTRACT Interleukin (IL)-18 acts in synergy with IL-12 to promote development of T helper 1 (Th1) responses. On the other hand, IL-18 alone has the capacity to induce Th2 responses. Here, we have measured IL-18 and IL-12 secretion by non-stimulated peripheral blood mononuclear cells (PBMC) from 17 non-pregnant women, 21 healthy pregnant women, 9 mildly pre-eclamptic patients and 15 severely pre-eclamptic patients. Th1/Th2 ratios in PBMC were determined by flow cytometry. PBMC from healthy pregnant subjects secreted more IL-18 and less IL-12 than non-pregnant women. PBMC from severely pre-eclamptic patients secreted more IL-12 than those from healthy pregnant women, while IL-18 secretion in mildly pre-eclamptic patients resembled that in normal pregnancy. The ratios of IL-18 to IL-12 were significantly higher in healthy pregnant women than non-pregnant women. These ratios were significantly lower in severely pre-eclamptic cases than in normal pregnancy subjects, while these ratios in mild pre-eclampsia resembled those in normal pregnancy. Interestingly, Th1/Th2 ratios were negatively correlated with the ratios of IL-18/IL-12. These results suggest that elevated IL-18 secretion and decreased IL-12 secretion by PBMC may induce Th2 dominance in normal pregnancy, while elevated secretion of both IL-18 and IL-12 by PBMC may cause Th1 dominance in severe pre-eclampsia.
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ABSTRACT: Our aim was to seek evidence for circulating leukocyte activation in preeclampsia. 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. 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. Normal third-trimester pregnancy is characterized by remarkable activation of peripheral blood leukocytes, which is further increased in preeclampsia.American Journal of Obstetrics and Gynecology 08/1998; 179(1):80-6. · 3.88 Impact Factor
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ABSTRACT: 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.American Journal of Obstetrics and Gynecology 03/1999; 180(2 Pt 1):499-506. · 3.88 Impact Factor
- Immunology Today - IMMUNOL TODAY. 01/1993; 14(7):335-338.
Journal of Reproductive Immunology
70 (2006) 163–164
Erratum to “The ratio of interleukin (IL)-18 to IL-12
secreted by peripheral blood mononuclear cells is
increased in normal pregnant subjects and
decreased in pre-eclamptic patients”
[Journal Reprod. Immunol. 61 (2004) 133–143]
Masatoshi Sakai, Arihiro Shiozaki, Yasushi Sasaki,
Satoshi Yoneda, Shigeru Saito∗
Department of Obstetrics and Gynecology, Toyama Medical and Pharmaceutical University, 2630 Sugitani,
Toyama-Shi, Toyama 930-0194, Japan
We published this paper in Journal of Reproductive Immunology 61 (2004) 133–143.
It has been pointed out that Figs. 2 and 4 in this paper are identical to Figs. 1 and 2 in
our previous paper in American Journal of Reproductive Immunology 47 (2002) 91–97
entitled ‘Interleukin-12 secretion by peripheral blood mononuclear cells is decreased
in normal pregnant subjects and increased in preeclamptic patients’. We apologise for
our accidental and careless mistake, and wish to replace Figs. 2 and 4 with the correct
Figs. 2 and 4. The patient numbers and the results were different between the two
In addition, the Results part of pages 136 and 137 should be changed to ‘IL-12 concen-
trations in culture supernatants of PBMC from non-pregnant women, healthy pregnancy
women, and mild and severe-type pre-eclamptic patients were 0.49±0.32pg/ml (range
0.1–1.05), 0.12±0.08pg/ml (range 01.–0.40), 0.20±0.24pg/ml (range 0.1–0.80) and
1.96±2.35pg/ml (range 0.1–8.40), respectively’ and ‘Th1/Th2 ratios in healthy pregnant
DOI of original article:10.1016/j.jri.2004.01.001.
∗Corresponding author. Tel.: +81 76 434 7355; fax: +81 76 434 5036.
E-mail address: firstname.lastname@example.org (S. Saito).
0165-0378/$ – see front matter © 2005 Elsevier Ireland Ltd. All rights reserved.
M. Sakai et al. / Journal of Reproductive Immunology 70 (2006) 163–164
Fig. 2. Secretion of IL-12 by cultured PBMC from non-pregnant women, healthy pregnant women and pre-
eclamptic patients. Vertical bars indicate the mean±S.D. Data were analyzed by the Mann–Whitney U-test.
indicate the mean±S.D. Data were analyzed by the Mann–Whitney U-test.
women were significantly lower than those in non-pregnant women (p=0.0437; Fig. 4).
These ratios in mild-type pre-eclamptic patients were significantly higher than those
in healthy pregnant women (p=0.0171), and were further elevated in severe-type pre-