TY  - JOUR
A1  - Glaser, Kirsten
A1  - Kern, David
A1  - Speer, Christian P.
A1  - Schlegel, Nicolas
A1  - Schwab, Michael
A1  - Thome, Ulrich H.
A1  - Härtel, Christoph
A1  - Wright, Clyde J.
T1  - Imbalanced inflammatory responses in preterm and term cord blood monocytes and expansion of the CD14\(^+\)CD16\(^+\) subset upon toll-like receptor stimulation
JF  - International Journal of Molecular Sciences
N2  - Developmentally regulated features of innate immunity are thought to place preterm and term infants at risk of infection and inflammation-related morbidity. Underlying mechanisms are incompletely understood. Differences in monocyte function including toll-like receptor (TLR) expression and signaling have been discussed. Some studies point to generally impaired TLR signaling, others to differences in individual pathways. In the present study, we assessed mRNA and protein expression of pro- and anti-inflammatory cytokines in preterm and term cord blood (CB) monocytes compared with adult controls stimulated ex vivo with Pam3CSK4, zymosan, polyinosinic:polycytidylic acid, lipopolysaccharide, flagellin, and CpG oligonucleotide, which activate the TLR1/2, TLR2/6, TLR3, TLR4, TLR5, and TLR9 pathways, respectively. In parallel, frequencies of monocyte subsets, stimulus-driven TLR expression, and phosphorylation of TLR-associated signaling molecules were analyzed. Independent of stimulus, pro-inflammatory responses of term CB monocytes equaled adult controls. The same held true for preterm CB monocytes—except for lower IL-1β levels. In contrast, CB monocytes released lower amounts of anti-inflammatory IL-10 and IL-1ra, resulting in higher ratios of pro-inflammatory to anti-inflammatory cytokines. Phosphorylation of p65, p38, and ERK1/2 correlated with adult controls. However, stimulated CB samples stood out with higher frequencies of intermediate monocytes (CD14\(^+\)CD16\(^+\)). Both pro-inflammatory net effect and expansion of the intermediate subset were most pronounced upon stimulation with Pam3CSK4 (TLR1/2), zymosan (TR2/6), and lipopolysaccharide (TLR4). Our data demonstrate robust pro-inflammatory and yet attenuated anti-inflammatory responses in preterm and term CB monocytes, along with imbalanced cytokine ratios. Intermediate monocytes, a subset ascribed pro-inflammatory features, might participate in this inflammatory state.
KW  - neonatal immunology
KW  - inflammation
KW  - preterm infants
KW  - monocytes
KW  - cord blood
KW  - monocyte subsets
KW  - cytokines
KW  - Toll-like receptor signaling
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-311056
SN  - 1422-0067
VL  - 24
IS  - 5
ER  - 
TY  - JOUR
A1  - Glaser, Kirsten
A1  - Speer, Christian P.
A1  - Wright, Clyde J.
T1  - Fine tuning non-invasive respiratory support to prevent lung injury in the extremely premature infant
JF  - Frontiers in Pediatrics
N2  - Within the last decades, therapeutic advances, such as antenatal corticosteroids, surfactant replacement, monitored administration of supplemental oxygen, and sophisticated ventilatory support have significantly improved the survival of extremely premature infants. In contrast, the incidence of some neonatal morbidities has not declined. Rates of bronchopulmonary dysplasia (BPD) remain high and have prompted neonatologists to seek effective strategies of non-invasive respiratory support in high risk infants in order to avoid harmful effects associated with invasive mechanical ventilation. There has been a stepwise replacement of invasive mechanical ventilation by early continuous positive airway pressure (CPAP) as the preferred strategy for initial stabilization and for early respiratory support of the premature infant and management of respiratory distress syndrome. However, the vast majority of high risk babies are mechanically ventilated at least once during their NICU stay. Adjunctive therapies aiming at the prevention of CPAP failure and the support of functional residual capacity have been introduced into clinical practice, including alternative techniques of administering surfactant as well as non-invasive ventilation approaches. In contrast, the strategy of applying sustained lung inflations in the delivery room has recently been abandoned due to evidence of higher rates of death within the first 48 h of life.
KW  - preterm infant
KW  - respiratory distress syndrome (RDS)
KW  - lung injury
KW  - bronchopulmonary dysplasia (BPD)
KW  - non-invasive ventilation
KW  - non-invasive respiratory support
KW  - continuous positive airway pressure (CPAP)
KW  - sustained lung inflation (SLI)
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193762
SN  - 2296-2360
VL  - 7
ER  -