Abstract
BackgroundAn altered amniotic cytokine profile has been reported in inflammatory pregnancy complications with a leading role for IL-6, a marker of the foetal systemic inflammatory response. Up to this date there is no exhaustive information neither on the foetal cytokine balance nor on the best method for its modulation. We aimed to evaluate the influence of vaginal lactoferrin administration on amniotic fluid concentration of 47 cytokines, chemokines and growth factors.MethodsSixty women undergoing genetic amniocentesis were enrolled in an open-label clinical trial. 300 mg of vaginal lactoferrin (Florence, Italy) were randomly administered to obtain 3 groups: A, 20 untreated patients; B and C (20 patients in each) respectively treated 4 and 12 h before amniocentesis. Cytokines, chemokines and growth factors concentrations were quantified by a magnetic bead Luminex multiplex immunoassays panel technology. Data analysis was performed with the software Stata (v. 13.1) and GraphPad Prism (v. 5). Group comparisons were performed using Kruskal–Wallis followed by Mann–Whitney U tests, with Bonferroni correction for multiple comparisons. A p < 0.05 was considered significant.ResultsAmong the 47 tested mediators, 24 (51.06%) were influenced by lactoferrin. 11 (23.4%), showed a highly significant difference (p <0.001); among these IL-9, IL-15, IFN-γ, IP-10, TNF-α, IL-1α and MCP-3 underwent a down-regulation, while IL-17 and FGF-basic, G-CSF, GM-CSF an up-regulation. Difference between group C and both B and A was small for IL-15, IP-10, IL-1α, MCP-3, while it was negligible for IL-9, IFN-γ and TNF-α. IL-17 and the 3 growth factors were strongly enhanced in B and C groups. IL-17, FGF-basic and GM-CSF showed increasing concentrations in both B and C groups, while G-CSF resulted up-regulated only in group C. Significance was intermediate (p < 0.01) for the down regulated IL-2RA, IL-12p40 and IFNα2 (6.38%) while it was small for 10 mediators (21.27%) 7 of which (IL-2, IL-4, eotaxin, PDGF-BB, RANTES, IL-18 and MIF) down-regulated and 3 (MCP-1, IL-3, and SDF-1α) up-regulated.ConclusionLactoferrin down-regulates 17 pro-inflammatory amniotic mediators while up-regulating 7 anti-inflammatory amniotic mediators, 5 of which definitively belonging to an anti-inflammatory profile. These findings open to clinical investigation on its use against inflammatory complications of pregnancy.
Highlights
An altered amniotic cytokine profile has been reported in inflammatory pregnancy complications with a leading role for IL-6, a marker of the foetal systemic inflammatory response
As for the foetal role, there is a large body of data on normal trophoblast function [2] as well as evidence indicating that foetal chromosomal abnormalities are characterized by alteration of some mediators of inflammation and coagulation which may explain the high incidence of early abortion linked with aneuploidy [3, 4]
No complications were registered within 7 days after amniocentesis, and the course of pregnancy was normal in all patients, ending in spontaneous delivery at term
Summary
An altered amniotic cytokine profile has been reported in inflammatory pregnancy complications with a leading role for IL-6, a marker of the foetal systemic inflammatory response. Successful pregnancy depends on an orderly production of trophoblast mediators aimed at modulating maternal adaptation, progressively increasing uterine-placental perfusion to draw substances for foetal growth. This task must be directly performed by the foetus, counteracting the natural reaction against the trophoblast induced uterine blood vessel rupture, that in any other tissue but uterus should activate inflammatory changes leading to coagulation and smooth muscle contraction. As for the foetal role, there is a large body of data on normal trophoblast function [2] as well as evidence indicating that foetal chromosomal abnormalities are characterized by alteration of some mediators of inflammation and coagulation which may explain the high incidence of early abortion linked with aneuploidy [3, 4]. Such evidence reinforces the concept of a direct foetal control on normal gestational processes
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