PLACENTAL INSUFFICIENCY, MELATONIN, PRO- AND ANTI-INFLAMMATORY CYTOKINES
DOI:
https://doi.org/10.11603/24116-4944.2018.1.7502Keywords:
melatonin, placenta, cytokines, intrauterine fetal growth restriction.Abstract
The aim of the study – to establish the correlation between the placental insufficiency and pro- and anti-inflammatory part of the immune system by studying of the levels of melatonin, pro- and anti-inflammatory cytokines in pregnant women with placental insufficiency.
Materials and Methods. 46 pregnant women with placental insufficiency were examined. The placental insufficiency manifested as the intrauterine growth restriction syndrome of fetus (IUGR) in the 3rd pregnancy trimester. Control group consisted of 20 women with uncomplicated pregnancy in the same term. The studying of the blood concentrations of melatonin, pro-inflammatory cytokines, such as tumor necrotizing factor-α (TNF-α), interleukin-1-β (IL-1-β), interleukin-6 (IL-6), and anti-inflammatory cytokines, such as interleukin-4 (IL-4) and interleukin-10 (IL-10), was conducted. The kit of reagents Melatonin ELISA, manufactured by IBL, Germany, was used for studying of the blood concentrations of melatonin. The levels of cytokines were determined in the blood using reagents manufactured by “Vektor-Best” (Ukraine).
Results and Discussion. It has been established that concentration of melatonin significantly decreases, if the pregnancy is complicated by intrauterine fetal growth restriction (study group – (126.87±14.87) pg/ml, control group – (231.25±21.56) pg/ml, p<0.001). The levels of pro-inflammatory cytokines in the study group were significantly higher, comparing with the control group (TNF-α: study group – (10.05±1.35) pg/ml, control group – (5.60±1.50) pg/ml, p<0.05; IL-1-β: study group – (14.67±2.13) pg/ml, control group – (3.96±0.92) pg/ml, p<0.001; IL-6: study group – (6.91±0.99) pg/ml, control group – (2.69±0.99) pg/ml, p<0.05). The same is true about anti-inflammatory cytokines (IL-4: study group – (5.97±0.50) pg/ml, control group – (3.74±0.62) pg/ml, p<0.05; IL-10: study group – (11.40±1.50) pg/ml, control group – (4.70±3.20) pg/ml, p<0.001).
Conclusions. The blood level of melatonin significantly decreases in case of placental insufficiency, manifested as intrauterine fetal growth restriction. The strengthening of the pro-inflammatory immunity, shown as the increasing of the levels of TNF-α, IL-1-β and IL-6, is also present in case of IUGR. The rising of the plasma concentration of the anti-inflammatory cytokines, such as IL-4 and IL-10, in our opinion, can be explained by activation of the mechanisms of compensation, which decrease the risk of premature labor.
References
Grishchenko, V.I. (1979). Rol epifiza v fiziologii i patologii zhenskoy polovoy sistemy [The role of epiphysis in the physiology and pathology of the female reproductive system]. Kharkiv: Vyshcha shkola [in Russian].
Shimada, M., Seki H., Samejima, M., Hayase, M. & Shirai, F. (2016). Salivary melatonin levels and sleep-wake rhythms in pregnant women with hypertensive and glucose metabolic disorders: A prospective analysis. BioSci. Trends, 10 (1), 34-41. DOI: 10.5582/bst.2015.01123
Soliman, A., Lacasse, A., Lanoix, D., Sagrillo-Fagundes, L., Boulard, V. & Vaillancourt, C. (2015). Placental melatonin system is present throughout pregnancy and regulates villous trophoblast differentiation. J Pineal Res., 59 (1), 38-46. DOI: 10.1111/jpi.12236
Takayama, H., Nakamura, Y., & Tamura, H. Pineal gland (melatonin) Affects the parturition time but not luteal function and fetal growth, in pregnant rats. Endocr. J., 50 (1), 37-43. DOI: 10.1507/endocrj.50.37
Teixeira, A.A., Simoes, M.J., Wanderley Teixeira, V., & Soares, J.Jr. (2004). Evaluation of the implantation in pinealectomized and/or submitted to the constant illumination rats. Int. J. Morphol., 22 (3), 189-194.
Richter, H.G., Hansell, J.A., Raut Sh, & Giussani, D.A. (2009). Melatonin improves placental efficiency and birth weight and increases the placental expression of antioxidant enzymes in undernourished pregnancy. J. Pineal. Res., 46, 357-364. DOI: 10.1111/j.1600-079X.2009.00671.x
Reiter, R.J., Dun Xian Tan, Korkmaz, A., & Rosales-Corral, S.A. (2013). Melatonin and stable circadian rhythms optimize maternal, placental and fetal physiology. Hum. Reprod. Update, 20 (2), 293-307. DOI: 10.1093/humupd/dmt054
Marseglia, L., D’Angelo, G., Manti, S., Reiter, R.J., & Gitto, E. (2016). Potential Utility of melatonin in preeclampsia, intrauterine fetal growth retardation, and perinatal asphyxia. Reprod. Sci., 23 (8), 970-977. DOI: 10.1177/1933719115612132
Esroy, O.F., Özkan, N., & Özsoy, Z. (2016). Effects of melatonin on cytokine release and healing of colonic anastomoses in an experimental sepsis model. Ulus Travma Acil Cerrahi Derg., 22 (4), 315-321. DOI: 10.5505/tjtes.2015.49465
Woo-Jin Yi, & Tae Sung Kim (2017). Melatonin protects mice against stress-induced inflammation through enhancement of M2 macrophage polarization. Int. Immunopharmacol., 48, 146-158. DOI: 10.1016/j.intimp.2017.05.006
Najafi, M., Shirazi, A., & Motevaseli, E. (2017). Melatonin as an anti-inflammatory agent in radiotherapy. Inflammopharmacol., 25 (4), 403-413. DOI: 10.1007/s10787-017-0332-5
Peraçoli, J.C., Rudge, M.V.C., & Peraçoli, M. (2007). Tumor necrosis factor-alpha in gestation and puerperium of women with gestational hypertension and pre-eclampsia. Am. Journ. Reprod. Immunol., 57, 177-185. DOI: 10.1111/j.1600-0897.2006.00455.x
Alijotas-Reig, J., Esteve-Valverde, E., Ferrer-Oliveras, R., Llurba, E., & Maria Gris, J. (2017). Tumor necrosis factor-alpha and pregnancy: focus on biologics. An updated and comprehensive review. Clinic Rev. Allerg. Immunol., 53 (1), 40-53. DOI: 10.1007/s12016-016-8596-x
Al-Azemi, M., Raghupathy, R., & Azizieh F. (2017) Pro-inflammatory and anti-inflammatory cytokine profiles in fetal growth restriction. Clin. and Exp. Obst. and Gyn., 44(1), 98–103.
Downloads
Published
How to Cite
Issue
Section
License
Authors who publish in this journal agree to the following terms:
1. The authors reserve the right to authorship of the work and pass the journal right of first publication of this work is licensed under a Creative Commons Attribution License, which allows others to freely distribute the work published with reference to the authors of the original work and the first publication of this magazine.
2. Authors are entitled to enter into a separate agreement on additional non-exclusive distribution of work in the form in which it was published in the magazine (eg work place in the electronic repository institution or publish monographs in part), provided that the reference to the first publication of this magazine.
3. Policy magazine allows and encourages authors placement on the Internet (eg, in storage facilities or on personal websites) manuscript of how to submit the manuscript to the editor and during his editorial processing, since it contributes to productive scientific discussion and positive impact on the efficiency and dynamics of citing published work (see. The Effect of Open Access).