Horm Metab Res 2005; 37(7): 419-424
DOI: 10.1055/s-2005-870231
Original Clinical
© Georg Thieme Verlag KG Stuttgart · New York

Interleukin-6 Concentrations in the Placenta and Blood in Normal Pregnancies and Preeclampsia

M.  Hayashi1 , Y.  Ueda2 , T.  Ohkura1 , N.  Inaba3
  • 1Department of Obstetrics and Gynecology, Koshigaya Hospital, Dokkyo University School of Medicine, Saitama, Japan
  • 2Department of Pathology, Koshigaya Hospital, Dokkyo University School of Medicine, Saitama, Japan
  • 3Department of Obstetrics and Gynecology, Dokkyo University School of Medicine, Tochigi, Japan
Further Information

Publication History

Received 22 November 2004

Accepted after revision 23 February 2005

Publication Date:
21 July 2005 (online)

Abstract

Aim: To evaluate whether IL-6 concentrations in the placenta and blood from women with preeclampsia differed from those in normal pregnancies. Methods: This study involved 41 pregnant women carrying single fetuses. Of these pregnancies, 23 were normal pregnant and 18 were preeclamptic patients. The average gestational age at entry was 37 - 38 weeks of gestation. Blood was collected before the onset of labor. Serum was separated and stored at - 20 °C. A tissue segment of the placenta was cut and chilled in liquid nitrogen immediately after delivery and stored at - 80 °C. The frozen tissue was added to phosphate-buffered saline and fully homogenized. After centrifugation, the separated supernatant was stored at - 80 °C. IL-6 levels in separated serum and IL-6 and total protein (TP) levels in separated supernatant were measured. The presence of IL-6 in the placenta was evaluated by immunohistochemistry in five preeclamptic and five normal pregnant patients. Results: Neither IL-6/TP levels in the placenta nor IL-6 levels in blood differed significantly between the two groups. IL-6 immunostaining on trophoblastic cells in the placenta was weak in one and absent in four in normal pregnancies, and absent in all patients with preeclampsia. There was no strong immunostaining for IL-6 in preeclampsia by immunohistochemistry. Conclusions: Our findings suggest that IL-6 in the placenta and blood does not play a significant role in the induction of an immunologic imbalance, which may contribute to the etiological mechanism leading to preeclampsia.

References

  • 1 Robertson S A, Seamark R F, Guilbert L J, Wegmann T G. The role of cytokines in gestation.  Crit Rev Immunol. 1994;  14 239-292
  • 2 Akira S, Taga T, Kishimoto T. Interleukin-6 in biology and medicine.  Adv Immunol. 1993;  54 1-78
  • 3 Saito S. Cytokine network at the feto-maternal interface.  J Reprod Immunol. 2000;  47 87-103
  • 4 Aderka D, Le J M, Vilcek J. IL-6 inhibits lipopolysaccharide-induced tumor necrosis factor production in cultured human monocytes, U937 cells, and in mice.  J Immunol. 1989;  143 3517-3523
  • 5 Kupferminc M J, Peaceman A M, Aderka D, Wallach D, Socol M L. Soluble tumor necrosis factor receptors and interleukin-6 levels in patients with severe preeclampsia.  Obstet Gynecol. 1996;  88 420-427
  • 6 Hayashi M, Numaguchi M, Ohkubo N, Yaoi Y. Blood macrophage colony-stimulating factor and thrombin-antithrombin III complex concentrations in pregnancy and preeclampsia.  Am J Med Sci. 1998;  315 251-257
  • 7 Hayashi M, Hoshimoto K, Ohkura T, Inaba N. Increased levels of macrophage colony-stimulating factor in the placenta and blood in preeclampsia.  Am J Reprod Immunol. 2002;  47 19-24
  • 8 Hayashi M, Numaguchi M, Watabe H, Yaoi Y. High blood levels of macrophage colony-stimulating factor in preeclampsia.  Blood. 1996;  88 4426-4428
  • 9 Hayashi M, Hamada Y, Ohkura T. Elevation of granulocyte-macrophage colony-stimulating factor in the placenta and blood in preeclampsia.  Am J Obstet Gynecol. 2004;  190 456-461
  • 10 Hayashi M, Ohkura T, Inaba N. Elevation of serum macrophage colony-stimulating factor before the clinical manifestations of preeclampsia.  Am J Obstet Gynecol. 2003;  189 1356-1360
  • 11 Hayashi M, Ohkura T. Elevated levels of serum macrophage colony-stimulating factor in normotensive pregnancies complicated by intrauterine fetal growth restriction.  Exp Hematol. 2002;  38 388-393
  • 12 Opsjon S L, Novick D, Wathen N C, Cope A P, Wallach D, Aderka D. Tumor necrosis factor, interleukin-1, and interleukin-6 in normal human pregnancy.  Am J Obstet Gynecol. 1993;  169 397-404
  • 13 Greer I A, Lyall F, Perera T, Boswell F, Macara L M. Increased concentrations of cytokines interleukin-6 and interleukin-1 receptor antagonist in plasma of women with preeclampsia: a mechanism for endothelial dysfunction?.  Obstet Gynecol. 1994;  84 937-940
  • 14 Conrad K P, Miles T M, Benyo D F. Circulating levels of immunoreactive cytokines in women with preeclampsia.  Am J Reprod Immunol. 1998;  40 102-111
  • 15 Johnson M R, Anim-Nyame N, Johnson P, Sooranna S R, Steer P J. Does endothelial cell activation occur with intrauterine growth restriction?.  Br J Obstet Gynaecol. 2002;  109 836-839
  • 16 Al-Othman S, Omu A E, Diejomaoh F M, Al-Yatama M, Al-Qattan F. Differential levels of interleukin 6 in maternal and cord sera and placenta in women with pre-eclampsia.  Gynecol Obstet Invest. 2001;  52 60-65
  • 17 Mushambi M C, Halligan A W, Williamson K. Recent developments in the pathophysiology and management of pre-eclampsia.  Br J Anaesth. 1996;  76 133-148
  • 18 Brosens I, Dixon H G, Robertson W B. Fetal growth retardation and the arteries of the placental bed.  Br J Obstet Gynaecol. 1977;  84 656-663
  • 19 Arnholdt H, Meisel F, Fandrey K, Lohrs U. Proliferation of villous trophoblast of the human placenta in normal and abnormal pregnancies.  Virchows Arch B Cell Pathol Incl Mol Pathol. 1991;  60 365-372
  • 20 Alvarez H, Benedetti W L, Morel R L, Scavarelli M. Trophoblast development gradient and its relationship to placental hemodynamics.  Am J Obstet Gynecol. 1970;  106 416-420
  • 21 Kauma S W, Wang Y, Walsh S W. Preeclampsia is associated with decreased placental interleukin-6 production.  J Soc Gynecol Investig. 1995;  2 614-617
  • 22 Kameda T, Matsuzaki N, Sawai K, Okada T, Saji F, Matsuda T, Hirano T, Kishimoto T, Tanizawa O. Production of interleukin-6 by normal human trophoblast.  Placenta.. 1990;  11 205-213

Masatoshi Hayashi, M.D., PhD

Department of Obstetrics and Gynecology, Koshigaya Hospital, Dokkyo University School of Medicine

2-1-50, Minami-Koshigaya · Koshigaya-shi · Saitama 343-8555 · Japan

Phone: +81-48-965-1111

Fax: +81-48-965-9326

Email: mhayashi@lilac.plala.or.jp

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