title: Influence of vaginal lactoferrin administration on amniotic fluid cytokines and its role against inflammatory complications of pregnancy.
abstract: BACKGROUND
  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. 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.
  
  
  METHODS
  Sixty 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. Ap< 0.05 was considered significant.
  
  
  RESULTS
  Among 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.
  
  
  CONCLUSIONS
  Lactoferrin 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.
authors.affiliation: Section of Infectious Diseases, Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Maritati
authors.affiliation: Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Trieste, Italy.
authors.forename: Manola
authors.initials: M
authors.lastname: Comar
authors.affiliation: Department of Medical Sciences, University of Trieste, Trieste, Italy.
authors.forename: Nunzia
authors.initials: N
authors.lastname: Zanotta
authors.affiliation: Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Trieste, Italy.
authors.forename: Silva
authors.initials: S
authors.lastname: Seraceni
authors.affiliation: Section of Medical Biochemistry, Molecular Biology and Genetics, Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Trentini
authors.affiliation: Obstetrics and Gynaecology Unit Hospital of Cento, Ferrara, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Corazza
authors.affiliation: Section of Obstetrics and Gynaecology, Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, I 44 100 Ferrara, Italy.
authors.forename: Fortunato
authors.initials: F
authors.lastname: Vesce
authors.affiliation: Section of Infectious Diseases, Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Contini
keywords: Abortion; Amniocentesis; Amniotic fluid; Cytokines; Inflammatory complications; Lactoferrin; Mediators; Pregnancy