The possible role of cytomegalovirus infection and pro-inflammatory IL_2 cytokine in preeclampsia
Keywords:Preeclampsia, CMV, IL-2 cytokine
Background and Objective: Fragmentary evidence suggests that trophoblast viral infection may play a role in placental dysfunction leading to complications like Preeclampsia. Among these, placental exposure to CMV induces an inflammatory response that precedes invasive trophoblast cell death. This study aimed to assess the frequency of anti-CMV IgG seropositivity and IL2 level in serum in patients with preeclampsia compared to normotensive control pregnant women.
Methods: A total of 90 women were enrolled, of which 60 had preeclampsia and 30 normotensive pregnant women as the control. A serum sample was collected from each subject and was investigated for anti-CMV IgG serostatus and IL-2 concentration using Enzyme-Linked Immunosorbent Assay (ELISA) based kits.
Results: In preeclamptic and normotensive pregnant women, 33.3% and 16.6% of the tested sera were seropositive for anti CMV IgG antibodies respectively (P = 0.136). Early onset preeclamptic women revealed a high frequency of anti-CMV seropositivity (80%) when compared with late onset Preeclampsia (20%). Cytokine assessment revealed a higher IL-2 level in preeclamptic women seropositive for anti-CMV IgG although statistically was not significant (P = 0.14), but in normotensive women, the IL-2 level was significantly higher in sera seropositive for anti-CMV IgG (P = 0.02).
Conclusion: This study delineates a high frequency of anti-CMV IgG antibodies particularly those with early onset preeclampsia; with no significant difference for the IL-2 level.
Schiessl B. Inflammatory response in preeclampsia. Mol Aspects Med 2007; 28:210-9.
Luppi P, Deloia JA. Monocytes of preeclamptic women spontaneously synthesize pro-inflammatory cytokines. Clin Immunology 2006; 118(2-3):268-5.
Xie F, Hu Y, Magee LA, Money DM, Patrick DM, Brunham RM, et al. Chlamydia pneumonia infection in preeclampsia. Hypertens Pregnancy 2010; 29:468-7.
Haggerty CL, Mark AK, Inge P, Soren AU, Debra CB, Jorn O. Prenatal Chlamydia trachomatis infection increase the risk of Preeclampsia. Hypertens Pregnancy 2013; 3: 151-1.
Tersigni C, Francesco F, Tullia T, Simona C, Giovanni S, Nicoletta DS. Insights into the Role of Helicobacter pylori infection in Preeclampsia: From the Bench to the Bedside. Front Immunol 2014; 5:484.
McDonnold M, Holly D, Ashley H, Luis DP, Gary DV, George RS, et al. High risk human papillomavirus at entry to prenatal care and risk of preeclampsia. Am J Obstet Gynecol 2014; 210:138-5.
Benyo DF, Smarason A, Redman CW, Sims C, Conrad KP. Expression of inflammatory cytokines in placentas from women with preeclampsia. J Clin Endocrinol Metab 2001; 86:2505-2.
Conrad JP, Benyo DF. Placental cytokines and the pathogenesis of preeclampsia. Am J Reprod Immunol 1997; 37:240-2.
Huang X, Hefeng H, Minyue D, Qiwei Y, Hanshi W. Serum and placental interleukin-18 are elevated in preeclampsia. J Reprod Immunol 2005; 65:77-8.
Sakai M, Hiroshi T, Kyoko T, Yasushi S, Shigeru S. Interleukin 12 secretions by peripheral blood mononuclear cells is decreased in normal pregnant subjects and increased in preeclamptic patients. Am J Reprod Immunol 2002; 47:91-9.
Lockwood CJ, Yen CF, Basar M, Kayisli UA, Martel M, Buhimschi I, et al. Preeclampsia related inflammatory cytokines regulate interkeukin-6 expression in human decidual cells. Am J Pathol 2008; 172:1571-9.
Wilczinski JR, Tchorzeski H, Banasik M. Lymphocyte subset distribution and cytokine secretion in third trimester decidua in normal pregnancy and preeclampsia. Eur J Obstet Gynecol Reprod Biol 2003; 109:8-1.
Kup Fermin MJ, Peaceman AM, Wigton TR, Tamura RK, Rehnbery KA, Socol ML. Immunoreactive tumor necrosis factor alpha is elevated in maternal plasma but undetected in amniotic fluid in the second trimester. Am J Obstet Gynecol 1994; 171(4):975-9.
Conrad KP, Miles TM, Benyo DF. Circulating level of immunoreactive cytokines in women with preeclampsia. Am J Repord Immunol 1998; 40(2):102-1.
Hill JA, Choi BC. Maternal immunological aspects of pregnancy success and failure. J Repord Fertili Suppl 2000; 55:91-7.
Doris C, Yujie M, Jian Z, Cindy M, Samuel P. Cytomegalovirus infection of trophoblast cells elicits an inflammatory response: A possible mechanism of placental dysfunction. Am J Obstet Gynecol 2006; 194:535-4.
Saito S, Sakai M, Sasaki Y, Tanebe K, Tsuda H, Michimata T. Quantitative analysis of peripheral blood THO, Th1, Th2 and Th1:Th2 cell ratio during normal human pregnancy and preeclampsia. Clin Exp Immunol 1999; 117:550-5.
Malek TR. The biology of interleukin 2. Annu Rev Immunol 2008; 26:453-4.
Hershko AY, Suzuki R, Charles N, Alvarez-Errico D, Sargent JL, Laurence A. Mast cell interleukin 2 production contributes to suppression of chronic allergic dermatitis. Immunity 2011; 35:562-5.
Liao W, Lin JX, Leonard WJ. Interleukin-2 at the Crossroads of Effectors Responses, Tolerance, and Immunotherapy. Immunity 2013; 38(1):13-25.
Romagnani S. T-cell subsets (Th1 versus Th2). Ann Allergy Asthma Immunol 2000; 85:9-18.
Almedia GD, Porada CD, Joers ST, Ascensao JL. Human cytomegalovirus alters interleukin-6 production by endothelial cells. Blood 1994; 83:370-6.
Cruz Spano L, Limma Pereira FE, Gomes da, Silva Basso N, Merco-de-Vargas PR. Human cytomegalovirus infection and abortion: an immunohistochemical study. Med Sci Monit 2002; 8:230-5.
Hamai Y, Fujii T, Yamashita T, Nishina H, Kozuma S, Mikami Y, et al. Evidence for an elevation in serum IL-2 and TNF-α level before the clinical manifestation of preeclampsia. Am J Repord Immunol 1997; 38:89-93.
Hamai Y, FuJii T, Yamashita T, Kozuma S, Okai T, Takrtani Y. Pathogenetic implication of IL-2 expressed in preeclamptic decidual tissue: a possible mechanism of deraned vasculature of placenta associated with preeclampsia. Am J Repord Immun1997; 38:83-8.
Fang X, Yuxiangu HU, Laura AM, Debora MM, David MP, MEL K, et al. An assciation between cytomegalovirus infection and preeclampsia: a case–control study and data synthesis. Acta Obstetricia et Gynecologica 2010; 89:1162-1.
ACOG Committee on Obstetric Practice. ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. American College of Obstetricians and Gynecologists. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 2002;100:847-59.
Gallersen B, Kemp F, Telgmeen R, DiMattia GE. Non-pituitary human prolactin gene transcription is independent of pit-1 and differentially controlled in lymphocytes and in endometrial stroma. Mol Endocrinol 1994; 8:356-3.
Abrahams VM, Visintia I, Aldo PB, Wuller S, Romer R, Mor G. A role for TLRs in the regulation of immune cell migration by first trimester trophoblast cells. J Immunol 2005;175(12):8096-104.
Kim Ym, Romero R, Oh SV, Kim CJ, Kilburn BA, Armant DR, et al. Toll-like receptor 4: a potential link between danger signals, the innate immune system and pre-eclampsia? Am J Obstet Gynecol 2005; 193:921-7.
Mazouni C, Capo C, Leda R. Honstettre A, Agostini A, Capelle M, Mege JL, Bretelle F. Pre-eclampsia: Impaired inflammatory response mediated by Toll-like receptor. J Repod Immunol 2008; 78:80-3.
Tanaka K, Yamada H, Minami M, Katoak S, Numazaki K, Minakami H. Screening for vaginal shedding of cytomegalovirus in healthy pregnant women using real-time PCR: Correlation of CMV in the vagina and adverse outcome of pregnancy. J Med Viral 2006; 78(6):757-9.
Von Dadelszen P, Megee LA. Could an infections trigger explain the differential maternal response to the shared placental pathology of preeclampsia and normotesive intrauterine growth restriction? Acta Obstet Gynecol Scand 2002; 81:642-8.
Xie F, Hu Y, Megee LA, Money DM, Patrick DM, Krajden M, et al. An association between cytomegalovirus infection and preeclampsia: a case control study and data synthesis. Acta Obstet Gynecol Scand 2010; 89:1162-7.
Von Dadelszen P, Magee LA, Krajden M, Alasaly K, Popovska V, Devarakonda RM, et al. Levels of antibodies against CMV an chamydophila pneumoniae are increased in early onset preeclampsia. BJOG 2003; 110:725-33.
Trogstand LI, Eskild A, Brau AL, Jeansson S, Jeaum PA. Is preeclampsia an infections disease? Acta Obstet Gynecol Scand 2001; 80:1036-8.
Gibson CS, Goldwater PN, MacLennan AH, Haan EA, Priest K, Dekker GA. Fetal exposure to herpes virus may be associated with pregnancy and preterm birth in a Caucasian population. BJOG 2008; 115:492-5.
Xie F, Hu Y, Megee LA, Thomas E, Von Dadelszen P. Increased Cytomegalovirus antibodies level and DNA loads in early onset of preeclampsia.197th ASM General Meeting Toronto, Canada 2007;117:99-8.
Strand KM, Odland ML, Iversen AC, Nordbo SA, Vik T, Austgulen R. Cytomegalovirus antibodies status at 17-18 weeks of gestation and preeclampsia: a case-control study of pregnant women in Norway. BJOG 2012; 119:1316-22.
Carreiras M, Montagnani S, Layriss Z. Preeclampsia: a multi factorial disease resulting from the interaction of the feto-maternal HLA genotypes and HCMV infection. Am J Reprod Immunol 2002; 48:176-8.
Fisher SO, Genbace VE, Maidji I, Pereira L. Human cytomegalovirus infection of placental cytotrophoblast in vitro and in utero: implication for transmission and pathogenesis. J Virology 2000; 74:6808-12.
Hamai Y, Fujii T, Yamashita T, Miki A, Hoyodo H, Kozuma S, et al. The expression of human leukocyte antigen-G on trophoblasts abolishes the growth- suppressing effect of interleukin-2 toward them. Am J Reprod Immunol 1999; 41:153-8.
Kumazaki K, Ozono K, Yahara T, Wada Y, Suehara N, Takeuchi M, Nakayama M. Detection of cytomegalovirus DNA in human placenta. J Med Virol 2002; 68:363-9.
Chou D, Ma Y, Oarry S. Cytomegalovirus shedding in early pregnancy is associated with preterm delivery [abstract]. Housty: J Soc Gynecol Investig 2004; 11:2-3.
Yamamoto-Tabata T, McDonagh S, Chang H, Fisher S, Pereira L. Human CMV interleukine-10 down regulates metalloproteinase activity and impairs endothelial cell migration and placental cytotrophoblast invasiveness in vitro. J Virol 2004; 78:2831-4.
Chan G, Hemmings D, Yurochko A, Guilbert L. Human cytomegalovirus-cause damaged to placental trophoblast mediated by immediate-early gene-induced tumor necrosis factor-α.. Am J Pathol 2002; 161:1371-8.
Grahame-Clarke C. Human cytomegalovirus, Endothelial Function and Atherosclerosis. HERPES 2005; 12(2):42-4.
How to Cite
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The copyright on any article published in Zanco J Med Sci is retained by the author(s) in agreement with the Creative Commons Attribution Non-Commercial ShareAlike License (CC BY-NC-SA 4.0).