PLACENTAL INSUFFICIENCY, MELATONIN, PRO- AND ANTI-INFLAMMATORY CYTOKINES

Authors

DOI:

https://doi.org/10.11603/24116-4944.2018.1.7502

Keywords:

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.

Published

2018-05-03

How to Cite

Berbets, A. M. (2018). PLACENTAL INSUFFICIENCY, MELATONIN, PRO- AND ANTI-INFLAMMATORY CYTOKINES. Actual Problems of Pediatrics, Obstetrics and Gynecology, (1). https://doi.org/10.11603/24116-4944.2018.1.7502

Issue

Section

OBSTETRICS AND GYNECOLOGY