PECULIARITIES OF THE CYTOKINE STATUS IN OBSTETRIC AND PERINATAL COMPLICATIONS IN WOMEN WITH INTRAHEPATIC CHOLESTASIS OF PREGNANCY
Abstract
Background. Intrahepatic cholestasis of pregnancy (COP) is the most common complication of pregnancy that occurs during the 2nd-3rd trimester and is accompanied by liver damage manifested as cholestasis and cytolysis.
Objective. To establish the role of cytokine response in the pathogenesis of COP as well as its obstetric and perinatal complications.
Material and methods. 87 pregnant women were examined: 57 with intrahepatic cholestasis of pregnancy and 30 patients of the comparison group. The levels of pro-inflammatory (interleukin 6) and anti-inflammatory (interleukin 4) cytokines were determined by enzyme-linked immunosorbent assay, and their prognostic significance as predictors of
obstetric and perinatal complications in women with COP was estimated.
Results. The course of COP is accompanied by a decrease in the concentrations of IL-6 and IL-4 cytokines and a lower ratio of IL-4/IL-6 (P(U)IL-6=0.041; P(U)IL-4=0.0007 and P(U)IL4/IL-6=0.008). The concentration of IL-6 in blood serum that is > 2.53 pg/ml (Se=83.3 %, Sp=73.9 %; AUC=0.822; 95 % CI 0.636–0.938; p=0.004) and IL-4 concentration that is > 41.99 pg/ml in symptomatic COP (Se=100.0 %, Sp=78.6 %; AUC=0.839; 95 % CI 0.593–0.965; p=0.011) are regarded as a risk factor for preterm labor (PL) in women with COP. The concentration of IL-6 > 3.07 pg/ml in women with COP and negative vaginal discharge culture can be considered as a predictor of meconium staining of amniotic fluid (MSAF) (Se=100.0 %, Sp=62.9 %; AUC=0.770; 95 % CI 0.597–0.895; p=0.024).
Conclusions. COP is accompanied by a lower level of IL-6; an atypical immune deviation with no shift towards the Th2 immune response that is characteristic of a normal pregnancy; as well as an imbalance in the cytokine response with a decrease in the anti-inflammatory link. Preterm birth in patients with COP is associated with higher levels of IL-6 during pregnancy. The release of meconium into amniotic fluid in women with COP (in the absence of significant pathogenic and opportunistic microflora according to the results of vaginal discharge culture) correlates with higher concentrations of IL-6 in the blood.
References
Kashtaljan OA, Ushakova LJu. Citokiny kak universalnaja sistema reguljacii [Cytokines as universal regulation system]. Medicinskie novosti. 2017;9:3-4. (Russian).
Druzhinina AS, Vitjazeva II. Patogeneticheskie osobennosti vlijanija immunologicheskih narushenij na rezultaty lechenija besplodija metodom jekstrakorporalnogo oplodotvorenija (JeKO) u zhenshhin reproduktivnogo vozrasta s nositelstvom antitel k tireoperoksidaze [Pathogenetic features of immunological disorders in women with thyroid peroxidase antibodies presence and their effect on infertility treatment by in vitro fertilization (IVF)]. Problemy jendokrinologii [Problems of Endocrinology]. 2019;65(4):289-294. https://doi.org/10.14341/probl10298 (Russian).
Dudareva JuA, Seroshtanova DN. Rol jendotelialnoj disfunkcii i subklinicheskogo vospalenija v razvitii akusherskih i perinatalnyh oslozhnenij u pacientok s saharnym diabetom [The role of endothelial dysfunction and subclinical inflammation in the development of obstetric and perinatal complications in diabetes mellitus patients]. Acta Biomedica Scientifica (East siberian biomedical journal). 2021;6(3):9-16. https://doi.org/10.29413/ABS.2021-6.3.1 (Russian).
Dzhabbarova JuK, Ismoilova ShT, Musahodzhaeva DA. Znachenie citokinov v patogeneze prejeklampsii u bere beremennyh s zhelezodeficitnoj anemiej [Importance of cytokines in the pathogenesis of preeclampsia in pregnant women with iron deficiency anemia]. Zhurnal akusherstva i zhenskih boleznej [Journal of obstetrics and womans diseases]. 2019;68(5):37-44. https://doi.org/10.17816/JOWD68537-44 (Russian).
Uspenskaja JuB, Sheptulin AA. Klinika, diagnostika i lechenie vnutripechenochnogo holestaza beremennyh [Clinical presentation, diagnosis and treatment of intrahepatic cholestasis of pregnancy]. Rossijskij zhurnal gastrojenterologii, gepatologii, koloproktologii [Russian Journal of Gastroenterology, Hepatology, Coloproctology]. 2017;27(4):96-101. https://doi.org/10.22416/1382-4376-2017-27-4-96-101. (Russian).
Turunen K, Sumanen M, Haukilahti R-L, Kirkinen P, Mattila K. Good pregnancy outcome despite intrahepatic cholestasis. Scand J Prim Health Care. 2010;28(2):102-107. https://doi.org/10.3109/02813431003784001
Ozkan S, Ceylan Y, Ozkan Veli O, Yildirim S. Review of a challenging clinical issue: Intrahepatic cholestasis of pregnancy. World J Gastroenterol. 2015;21(23):7134-7141. https://doi.org/10.3748/wjg.v21.i23.7134
