Research Communication Elevated Circulating IL-1β and TNF-Alpha, and Unaltered IL-6 in First-Trimester Pregnancies Complicated by Threatened Abortion With an Adverse Outcome
Nicolaos Vitoratos, Constantinos Papadias, Emmanuel Economou, Evangelos Makrakis, ConstantinosPanoulis, and George Creatsas
2nd Department of Obstetrics and Gynecology, Medical School, University of Athens, Aretaieion Hospital, 115 28 Athens, Greece Received 14 November 2005; Revised 29 March 2006; Accepted 30 March 2006 The purpose of the present study was to examine the proﬁle of selected proinﬂammatory cytokines in maternal serum of ﬁrsttrimester pregnancies complicated by threatenedabortion (TACP) and its relevance to obstetric outcome. Serum levels of Th1type cytokines interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-alpha), and Th2-type cytokine interleukin 6 (IL-6) were measured, by ELISA, in 22 women with TACP and adverse outcome at admission (group A) and compared with the corresponding levels of 31 gestational age-matched women with TACP and successful outcome atadmission (group B1) and discharge (group B2) and 22 gestational age-matched women with ﬁrst-trimester uncomplicated pregnancy (group C) who served as controls. Mann-Whitney U or Wilcoxon test was applied as appropriate to compare diﬀerences between groups. IL-1β and TNF-alpha were detected with signiﬁcantly higher levels in group A, compared to all other groups. On the contrary, IL-6 levels weredetected with no signiﬁcant diﬀerence among all the other groups studied. It is concluded that in ﬁrst-trimester TACP with adverse outcome, a distinct immune response, as reﬂected by elevated maternal IL-1β, TNF-alpha, and unaltered IL-6 levels, is relevant to a negative obstetric outcome. Copyright © 2006 Nicolaos Vitoratos et al. This is an open access article distributed under the CreativeCommons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
INTRODUCTION Spontaneous abortion is the loss of an intrauterine pregnancy without outside intervention before 20 weeks’ gestation and can be subdivided into threatened abortion, inevitable abortion, incomplete abortion, missed abortion, septicabortion, complete abortion, and recurrent spontaneous abortion . Threatened abortion refers to an intrauterine viable clinical pregnancy accompanied by an intrauterine source of painless vaginal bleeding and successful or adverse pregnancy outcome . The cytokine network has been suggested to be involved with positive or negative evolution of the ongoing pregnancies . Prevalence of Th2-typecytokines (secreted by Thelper 2 cells and certain antigen-presenting cells (APCs)) may be associated with successful pregnancy; whereas the dominance of Th1-type cytokines (derived from T-helper 1 cells and APCs) may be indicative of a pathological pregnancy both in experimental animals and in humans [4, 5]. IL-1β is an essential proinﬂammatory, Th1-type cytokine, produced by monocytes,macrophages, and epithelial
cells. Its secretion leads to production of tumor necrosis factor (TNF-alpha), interferon (IFN-γ), IL-2, and IL12 , uterotonic prostaglandin E2 and/or matrix metalloproteinases by fetal membrane cells, as well as to promotion of apoptotic cell death in fetal membrane tissues . Due to these properties, IL-1β may express abortogenic action. On the other side, elevatedIL-1β levels may increase the likelihood of successful and complete implantation, and, during the ﬁrst trimester, may also oﬀer the fetus increased protection against microbial pathogens that were present in the uterus before the conception period, during the conception period, or in the early postconception period . TNF-alpha, a Th1-type cytokine, is mainly produced by mononuclear phagocytes,...