The role of cytokines in the perinatal period

Protonotariou E1, Rizos D1, Τrakakis E2, Sarantakou A1, Salamalekis E2

1Hormone Laboratory, Aretaieio University Hospital, Athens, Greece.

23rd Obstetrics and Gynecological Clinic, Athens University, ATTIKON hospital, Athens, Greece. 

Correspondence: A. Sarantakou, 101 Ivis st, 17561,  P. Faliro, Greece. 

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Abstract

Selected cytokines, as: Inteleukin-2 (IL-2), interferon-γ (IFN- γ), interleukin-4 (IL-4), interleukin-1β (IL-β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and their soluble receptors: sIL-2R sIL- 4R, sIL-6R, sTNF RI and sTNF RII were studied during parturition and early life, in order to identify their role in initiation of normal labour and development of immune response after birth. Fifty-five healthy pregnant women, their healthy full-term neonates and 45 females and males, as control-adults were included in the study. Cytokine concentrations were determined in maternal serum (MS), umbilical cord (UC), the neonates, on 1st (1N) and 5th (5N) day after birth, and in adults, using ultra-sensitive enzyme-immunoassays. IL-2 and IL-4 concentrations in UC are significantly higher, compared to those in adults and MS (p<0.01, p<0.0001). IL-2 values decrease significantly on the 5th day (p<0.01), while those of IL-4 remain in the same levels. On the contrary, IFN-γ values in UC are significantly lower, than those in adults and MS (p<0.04), increasing however significantly on the 5th day of life (p<0.03). Neonatal serum values of sIL-2R and sIL-4R are markedly elevated, compared to adults’ and MS values (p<0.4, p<0.0001). IL-1β, IL-6, TNF-α, sIL-6R, sTNF-RI and sTNFRII concentrations in MS (except TNF-α), and neonatal serum are significantly higher, than those in adults (p<0.05, p<0.0001), while IFN-γ, IL-1β, IL-6, TNF-α, IL-2R, IL-4R and sTNF-RI concentrations in MS and/or neonatal samples are strongly correlated with mode of delivery, with significantly higher values in normal labor, compared to elected caesarean section (p<0.01, p<0.0001). The results of this study indicate: a) Enhanced expression of IL-2 and IL-4, against IFN-γ at birth  that seems to be regulated during the early neonatal life, suggesting a developmental phenomenon in ontogeny of the immune system. b) Involvement of inflammatory cytokines in the initiation of labor and in activation  of neonatal immune response. c) Important role for soluble receptors of inflammatory cytokines in the regulation  of immune response in labour and early life.

Key words: IL-2; IL-4; IL-6; IL-1β; INF-γ; sIL-2R; sIL-4R; sIL-6R; sTNF RI; sTNF RII; TNF-α.