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Cytokine mapping of sera from women with preeclampsia and from women with normal pregnancies
Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology . Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology . Linköping University, Faculty of Health Sciences.
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2006 (English)In: Journal of Reproductive Immunology, ISSN 0165-0378, Vol. 70, no 1-2, 83-91 p.Article in journal (Refereed) Published
Abstract [en]

Introduction

Preeclampsia is a pregnancy-specific syndrome. The immune system in preeclampsia is changed with an increased innate activity and there is a hypothesis of a shift towards Th1-type immunity. The aim of this study was to determine a spectrum of soluble immunological factors denoting different aspects of immune activation in third trimester sera from women with preeclampsia (N = 15) and compare with levels in sera from normal pregnant women (N = 15).

Material and methods

IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 p40, IL-13, IL-15, IL-17, IFN-α, IFN-γ, TNF-α, GM-CSF, MIP-lα, MIP-1β, MCP-1, eotaxin and RANTES were measured in serum using multiplex bead arrays. The levels of soluble CD14 and soluble IL-4 receptor were measured by enzyme-linked immunoassay (ELISA).

Results

Preeclamptic women had significantly increased levels of circulating IL-6 (p = 0.002), IL-8 (p = 0.003) and soluble IL-4R (p = 0.037), compared to women with normal pregnancies.

Conclusion

This study supports the hypothesis of increased inflammatory responses in preeclampsia, illustrated by the increased levels of IL-6 and IL-8. The finding of increased levels of soluble IL-4 receptor is an intriguing finding with several interpretations, which may partly support the hypothesis of a Th1 shift in preeclampsia.

Place, publisher, year, edition, pages
2006. Vol. 70, no 1-2, 83-91 p.
Keyword [en]
Cytokines; Serum; Multiple bead array; Preeclampsia
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-14374DOI: 10.1016/j.jri.2005.10.007OAI: oai:DiVA.org:liu-14374DiVA: diva2:23352
Available from: 2007-03-23 Created: 2007-03-23 Last updated: 2013-08-29
In thesis
1. Cytokines and immune balance in preeclampsia: a survey of some immunological variables and methods in the study of preeclampsia
Open this publication in new window or tab >>Cytokines and immune balance in preeclampsia: a survey of some immunological variables and methods in the study of preeclampsia
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Preeclampsia is one of the most feared pregnancy complications, with a risk of maternal and fetal death and with no ideal therapy readily available. The cause of this strictly pregnancyrelated disease is still unknown and is therefore a great challenge to all researchers in the field of pregnancy-related pathophysiology.

Today, the dominating theory of the origin of preeclampsia is defective initial placentation with insufficient penetration of the trophoblasts, leading to impaired maternal blood flow through narrow spiral arteries. However, the cause of this defective trophoblast behavior is not known. The maternal immune system has been proposed to have an influence on both the placentation and the subsequent systemic reactions. Therefore, it is very interesting to study the maternal immune system during preeclampsia, in hope of achieving a better understanding of this puzzling disease.

Earlier studies have suggested that normal pregnancy requires a shift to a Th2/antiinflammatory type of immunity, at least directed towards the fetus and placenta, while some pregnancy complications, such as preeclampsia, could be due to a skewed Th1/proinflammatory type of immunity. However, the results from earlier studies designed to test the Th1/Th2 hypothesis in preeclampsia have not been consistent. Therefore, the aim of this thesis was to examine if established preeclampsia is associated with increased innate inflammatory responses and a deviation of adaptive responses towards Th1 when compared with normal pregnancy.

Enumerations of cytokine-producing cells from peripheral blood did not show any difference in the production of IFN-γ, IL-4, IL-10 and IL-12 between women with preeclampsia and normal pregnancies. However, a decrease in the spontaneously produced levels of IL-5 was detected in cell cultures on peripheral blood mononuclear cells in women with preeclampsia. Furthermore, a decreased production of IL-10 in response to paternal antigens, believed to represent the fetus, was also detected for the preeclamptic women.

Serum analysis showed increased levels of the pro-inflammatory mediators IL-6 and IL-8 during preeclampsia. Also, preeclamptic women displayed increased serum levels of the soluble IL-4 receptor, but no difference in the levels of IL-4 compared to normal pregnant women. This was an elusive finding, since the receptor was originally thought to reflect the levels of IL-4, but has recently been shown to have both agonistic and antagonistic properties on the IL-4 levels. Further studies of the local immune responses in the placenta showed no difference in the immunohistochemical staining of IL-4 and TNF-α between women with preeclampsia and women with normal pregnancies. In general, there were no hallmarks of abnormal morphology in the placental sections examined, regardless of diagnosis.

In conclusion, the decreased levels of IL-10 in response to paternal antigens and the systemically increased levels of IL-6 and IL-8 suggest a specific decrease in antiinflammatory responses towards fetal antigens, together with a systemic activation of proinflammatory mediators during preeclampsia. Furthermore, the decreased production of IL-5 also indicates, at least partly, decreased Th2 responses in the established preeclampsia.

Place, publisher, year, edition, pages
Institutionen för molekylär och klinisk medicin, 2005
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 924
Keyword
Preeclampsia, Cytokines, Leukocytes, Immunology, Placenta, Th1/Th2 balance, Inflammation
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:liu:diva-8602 (URN)91-85497-60-6 (ISBN)
Public defence
2005-12-09, Berzeliussalen, Campus Valla, Linköpings universitet, Linköping, 13:00 (English)
Opponent
Supervisors
Note
Figure 1 on page 6 is republished in the Ph.D. thesis with the kind permisson of Blackwell Publishing (http://www.blackwellpublishing.com). Figure IX on page38, figure XB on page 41, figure XI on page 46 and figure XII on page 47 are all published in the Journal of Reproductive Immunology and republished with kind permisson from Elsevier (http://www.elsevier.com/) in the Ph.D. thesis.Available from: 2007-03-23 Created: 2007-03-23 Last updated: 2013-08-29

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Jonsson, YvonneRubér, MarieMatthiesen, LeifBerg, GöranNieminen, KatriErnerudh, JanEkerfelt, Christina

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