Cyclic AMP in human preterm infant blood is associated with increased TLR-mediated production of acute-phase and anti-inflammatory cytokines in vitro.
Cells, Cultured
Chorioamnionitis
/ blood
Cyclic AMP
/ blood
Cytokines
/ blood
Diglycerides
/ pharmacology
Female
Fetal Blood
/ immunology
Gestational Age
Humans
Infant, Newborn
Infant, Premature
/ blood
Inflammation Mediators
/ blood
Leukocytes
/ drug effects
Lipopolysaccharides
/ pharmacology
Longitudinal Studies
Male
Oligopeptides
/ pharmacology
Pregnancy
Prospective Studies
Toll-Like Receptors
/ agonists
Journal
Pediatric research
ISSN: 1530-0447
Titre abrégé: Pediatr Res
Pays: United States
ID NLM: 0100714
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
30
05
2018
accepted:
21
08
2019
revised:
16
08
2019
pubmed:
3
10
2019
medline:
29
9
2021
entrez:
3
10
2019
Statut:
ppublish
Résumé
Preterm infants are at high risk of infection and have distinct pathogen recognition responses. Suggested mechanisms include soluble mediators that enhance cellular levels of cAMP. The aim of this study was to assess the relationship between blood cAMP concentrations and TLR-mediated cytokine production in infants during the first month of life. Cord and serial peripheral blood samples (days of life 1-28) were obtained from a cohort of very preterm (<30 weeks' gestational age) and term human infants. Whole-blood concentrations of cAMP and FSL-1 and LPS in vitro stimulated cytokine concentrations were measured by ELISA and multiplex bead assay. cAMP concentrations were higher in cord than in peripheral blood, higher in cord blood of female preterm infants, and lower at Days 1 and 7 in infants exposed to chorioamnionitis, even after adjusting for leukocyte counts. TLR2 and TLR4-mediated TNF-α, IL-1β, IL-6, IL-12p70, and IL-10 production in vitro increased over the first month of life in preterm infants and were positively correlated with leukocyte-adjusted cAMP levels and reduced by exposure to chorioamnionitis. The ontogeny of blood cAMP concentrations and associations with chorioamnionitis and TLR-mediated production of cytokines suggest that this secondary messenger helps shape distinct neonatal pathogen responses in early life.
Sections du résumé
BACKGROUND
Preterm infants are at high risk of infection and have distinct pathogen recognition responses. Suggested mechanisms include soluble mediators that enhance cellular levels of cAMP. The aim of this study was to assess the relationship between blood cAMP concentrations and TLR-mediated cytokine production in infants during the first month of life.
METHODS
Cord and serial peripheral blood samples (days of life 1-28) were obtained from a cohort of very preterm (<30 weeks' gestational age) and term human infants. Whole-blood concentrations of cAMP and FSL-1 and LPS in vitro stimulated cytokine concentrations were measured by ELISA and multiplex bead assay.
RESULTS
cAMP concentrations were higher in cord than in peripheral blood, higher in cord blood of female preterm infants, and lower at Days 1 and 7 in infants exposed to chorioamnionitis, even after adjusting for leukocyte counts. TLR2 and TLR4-mediated TNF-α, IL-1β, IL-6, IL-12p70, and IL-10 production in vitro increased over the first month of life in preterm infants and were positively correlated with leukocyte-adjusted cAMP levels and reduced by exposure to chorioamnionitis.
CONCLUSIONS
The ontogeny of blood cAMP concentrations and associations with chorioamnionitis and TLR-mediated production of cytokines suggest that this secondary messenger helps shape distinct neonatal pathogen responses in early life.
Identifiants
pubmed: 31578034
doi: 10.1038/s41390-019-0586-2
pii: 10.1038/s41390-019-0586-2
pmc: PMC7392158
mid: NIHMS1540546
doi:
Substances chimiques
Cytokines
0
Diglycerides
0
FSL-1 lipoprotein, synthetic
0
Inflammation Mediators
0
Lipopolysaccharides
0
Oligopeptides
0
Toll-Like Receptors
0
Cyclic AMP
E0399OZS9N
Types de publication
Journal Article
Observational Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
717-725Subventions
Organisme : NIAID NIH HHS
ID : R01 AI067353
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI100135
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI124284
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI118608
Pays : United States
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