Influence of vaginal lactoferrin administration on amniotic fluid cytokines and its role against inflammatory complications of pregnancy

Martina Maritati, Manola Comar, Nunzia Zanotta, Silva Seraceni, Alessandro Trentini, Fabrizio Corazza, Fortunato Vesce, Carlo Contini

Research output: Contribution to journalArticle

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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. A p < 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. Conclusion: 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.

Original languageEnglish
Article number5
JournalJournal of Inflammation (United Kingdom)
Volume14
Issue number1
DOIs
Publication statusPublished - Feb 15 2017

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Intravaginal Administration
Lactoferrin
Pregnancy Complications
Amniotic Fluid
Interleukin-17
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-9
Cytokines
Interleukin-15
Intercellular Signaling Peptides and Proteins
Amniocentesis
Fluids
Interleukin-3
Granulocyte Colony-Stimulating Factor
Interleukin-1
Chemokines
Anti-Inflammatory Agents
Down-Regulation
Interleukin-12 Subunit p40
Chemokine CCL5

Keywords

  • Abortion
  • Amniocentesis
  • Amniotic fluid
  • Cytokines
  • Inflammatory complications
  • Lactoferrin
  • Mediators
  • Pregnancy

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology

Cite this

Influence of vaginal lactoferrin administration on amniotic fluid cytokines and its role against inflammatory complications of pregnancy. / Maritati, Martina; Comar, Manola; Zanotta, Nunzia; Seraceni, Silva; Trentini, Alessandro; Corazza, Fabrizio; Vesce, Fortunato; Contini, Carlo.

In: Journal of Inflammation (United Kingdom), Vol. 14, No. 1, 5, 15.02.2017.

Research output: Contribution to journalArticle

Maritati, Martina ; Comar, Manola ; Zanotta, Nunzia ; Seraceni, Silva ; Trentini, Alessandro ; Corazza, Fabrizio ; Vesce, Fortunato ; Contini, Carlo. / Influence of vaginal lactoferrin administration on amniotic fluid cytokines and its role against inflammatory complications of pregnancy. In: Journal of Inflammation (United Kingdom). 2017 ; Vol. 14, No. 1.
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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. A p < 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. Conclusion: 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.",
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T1 - Influence of vaginal lactoferrin administration on amniotic fluid cytokines and its role against inflammatory complications of pregnancy

AU - Maritati, Martina

AU - Comar, Manola

AU - Zanotta, Nunzia

AU - Seraceni, Silva

AU - Trentini, Alessandro

AU - Corazza, Fabrizio

AU - Vesce, Fortunato

AU - Contini, Carlo

PY - 2017/2/15

Y1 - 2017/2/15

N2 - 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. A p < 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. Conclusion: 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.

AB - 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. A p < 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. Conclusion: 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.

KW - Abortion

KW - Amniocentesis

KW - Amniotic fluid

KW - Cytokines

KW - Inflammatory complications

KW - Lactoferrin

KW - Mediators

KW - Pregnancy

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