Dominance of Pro-Inflammatory Cytokines Over Anti-Inflammatory Ones in Placental Bed of Creta Cases

The objective of the study is to investigate changes occurring in key inflammatory cytokines at molecular level (including genetic and protein) in placental bed of placenta creta compared to that of normal placenta and their correlation to interstitial extravillous trophoblasts (EVT) number. Case-control study including placentas of patients with invasive placentation (creta placentas, = 19) compared with those of normal placentation ( = 19). Besides routine histology and immunocytochemistry detection (cytokeratin-7 [CK-7]), addition to biochemical evaluation of expression of various cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), IL6, IL-1RA, IL-8, IL-10, and IL-13 was carried out. Routine histological examination of placentas of creta cases revealed CK-7 extravillous trophoblasts (EVT) penetrating deeply the myometrium with various histopathological arrangements and trophoblastic vascular invasion of the deep myometrial blood vessels. A significant increase ( < 0.05) in the mRNA expression of TNF-α, IL-1 β, and IL6 with an insignificant decrease in placental bed IL-1RA, IL-8, IL-10, and IL-13 was observed in creta cases compared to the control ones. A corresponding significant increase was detected in the protein levels of TNF-α, IL-1 β, and IL-6 as well as an insignificant decrease in placental bed IL-1RA, IL-8, IL-10, and IL-13 in creta cases compared to the normal ones. Moreover, we displayed a significant positive correlation ( < 0.05) between interstitial EVT number and mRNA expression of almost all pro-inflammatory cytokines with negative but insignificant correlation with anti-inflammatory cytokines in creta cases. The upregulated pro-inflammatory cytokines and the correlation of their expression with the increased interstitial EVT provide a supporting evidence of their potentially more relevant role in the development of placenta creta than the anti-inflammatory ones.