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Indications of an altered immune balance in preeclampsia: A decrease in in vitro secretion of IL-5 and IL-10 from blood mononuclear cells and in blood basophil counts compared with normal pregnancy
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.
Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
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2005 (English)In: Journal of Reproductive Immunology, ISSN 0165-0378, Vol. 66, no 1, 69-84 p.Article in journal (Refereed) Published
Abstract [en]

It has been suggested that maladaptation of the maternal immune response during pregnancy might be a causal factor for preeclampsia. This study was designed to examine the systemic immune status at both the innate level and the adaptive level in pregnancies complicated by preeclampsia (n = 15) and normal pregnancies (n = 15). Spontaneous and in vitro-induced secretion of IL-5, IL-6, IL-10, IL-12, IL-13 and TNF-α, in response to paternal blood cells and the vaccination antigens purified protein derivate of tuberculin (PPD) and tetanus toxoid (TT), was detected in cell culture supernatants from blood mononuclear cells by ELISA. Preeclamptic women showed reduced numbers of basophil granulocytes in the blood (p = 0.004) and lower spontaneous secretion of IL-5 from blood mononuclear cells (p = 0.016). In addition, paternal antigen-induced secretion of IL-10 was decreased in preeclampsia compared with normal pregnancy (p = 0.012). No further differences between preeclampsia and normal pregnancy were found for any stimuli or cytokines. The present findings of reduced basophil numbers and lower spontaneous in vitro secretion of IL-5 in preeclampsia compared with normal pregnancy indicate a decrease in systemic Th2 immunity in preeclampsia. Furthermore, the decrease in paternal antigen-induced secretion of the immunosuppressive cytokine IL-10 in preeclampsia indicates a fetus-specific decrease in immunosuppression mediated by blood mononuclear cells. Whether these systemic changes are a cause or a consequence of preeclampsia remains to be elucidated.

Place, publisher, year, edition, pages
2005. Vol. 66, no 1, 69-84 p.
Keyword [en]
Cytokines; Preeclampsia; In vitro; ELISA; Th1/Th2
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-14373DOI: 10.1016/j.jri.2005.02.002OAI: oai:DiVA.org:liu-14373DiVA: diva2:23351
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)
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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, YvonneMatthiesen, LeifBerg, GöranErnerudh, JanNieminen, KatriEkerfelt, Christina

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