Melatonin decreases and cytokines increase in women with placental insufficiency

Purpose: To investigate the levels of melatonin, proinflammatory and anti-inflammatory cytokines in pregnant women with placental insufficiency (PI). Materials and Methods: The PI was manifested as the intrauterine growth restriction syndrome of fetus (IUGR) in the third pregnancy trimester. The control group consisted of 20 women with uncomplicated pregnancy in the same term. The blood concentrations of melatonin, proinflammatory cytokines, such as tumor necrotizing factor-alpha (TNF-alpha), interleukin-1-beta (IL-1-beta), interleukin-6 (IL-6), and anti-inflammatory cytokines, such as interleukin-4 (IL-4), and interleukin-10 (IL-10), were studied. Results: The concentration of melatonin was found to decrease significantly if pregnancy was complicated by intrauterine fetal growth retardation (study group -126.87 +/- 14.87 pg/ml, control group -231.25 +/- 21.56 pg/ml, p < .001). The levels of proinflammatory cytokines in the study group were significantly higher as compared with the control group (TNF-alpha: study group -10.05 +/- 1.35 pg/ml, control group -5.60 +/- 1.50 pg/ml, p < .05; IL-1-beta: study group -14.67 +/- 2.13 pg/ml, control group -3.96 +/- 0.92 pg/ml, p < .001; IL-6: study group -6.91 +/- 0.99 pg/ml, control group -2.69 +/- 0.99 pg/ml, p < .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 < .05; IL-10: study group -11.40 +/- 1.50 pg/ml, control group -4.70 +/- 3.20 pg/ml, p < .001). A moderate negative correlation between melatonin and IL-1-beta in the group with PI (r = -0.3776, p = .0097), a closed negative correlation between the same indexes in the control group (r = -0.6785, p = .001), and a moderate negative correlation between melatonin and TNF-alpha (r = -0.4908, p = .02) were found. Conclusions: The blood level of melatonin significantly decreases in case of placental insufficiency, manifested as intrauterine fetal growth restriction. Strengthening of the proinflammatory immunity shown as the increasing of the levels of TNF-alpha, IL-1-beta, and IL-6 levels is also present in case of IUGR. Increase of the serum concentration of the anti-inflammatory cytokines, such as IL-4 and IL-10, in our opinion, can be explained by activation of compensatory mechanisms, which decrease the risk of premature labor.