Impact of histological chorioamnionitis on tracheal aspirate cytokines in premature infants.
ABSTRACT Histological chorioamnionitis (CHORIO) may increase inflammatory mediators in the lungs of preterm infants.
To study the impact of CHORIO on tracheal aspirate (TA) cytokines in ventilated infants.
TA samples collected within 48 hours after birth from 40 ventilated neonates (gestational age [GA] <30 weeks, body weight [BW] <1250 g) were analyzed. Levels of 12 cytokines (interleukin [IL]-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, epidermal growth factor [EGF], interferon-γ [IFN-γ], monocyte chemotactic protein-1 [MCP-1], tumor necrosis factor-α [TNF-α], vascular endothelial growth factor [VEGF]) were measured using a biochip multianalyte immunoassay (Randox Laboratories, Antrim, UK). Total protein was measured by the Bradford assay. CHORIO assessment was done by a blinded pathologist.
Twenty-six infants (GA 26.6 ± 1.4 weeks, BW 852 ± 162 g) had no CHORIO and 14 (GA 25.1 ± 1.0 weeks, BW 776 ± 164 g) had CHORIO. IL-1α, IL-1β, IL-8, and VEGF were significantly higher in TA of infants with CHORIO. After correction for dilution, IL-1α, IL-1β, and IL-8 were significantly elevated. Increased TA total cell count correlated with CHORIO, VEGF, EGF, MCP-1, IL-8, and IL-6 TA levels (all p ≤ 0.02). Ventilator, oxygen supplementation, and hospital days correlated with TA IFN-γ levels (all p ≤ 0.01).
CHORIO is associated with increased specific proinflammatory mediators in TA samples of preterm infants.
- Hypertension 10/2013; · 7.63 Impact Factor
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ABSTRACT: Funisitis reflects the fetal systemic inflammatory response in premature infants. Macrophages and neutrophils have been identified as key elements in the inflammatory process of the lungs, and secrete proteases that cause the destruction of the extracellular matrix (ECM). Fibronectin (FN) is the major constituent of the pulmonary ECM and exists in multiple isoforms arising from alternative RNA splicing. Extra domain A (EDA) is the major alternatively spliced segment, and the expression of EDA containing FN (EDA + FN) in the lungs is associated with distal pulmonary cell proliferation during alveolar formation. To study the relationship between the presence of funisitis and EDA + FN levels in the tracheal aspirate fluid (TAF) of infants of less than 28 weeks' gestation. The subjects included in this study were 26 extremely premature infants of <28 weeks' gestation at <24 hr of age, from whom the TAF was collected. These preterm infants were divided into two groups according to placental histology. The funisitis (+) group (n = 9) was compared with the funisitis (-) group (n = 17). The TAF supernatants were analyzed for IL-1β, IL-6, IL-8, neutrophil elastase, and EDA + FN using enzyme-linked immunosorbent assay (ELISA). There were no significant differences in gestational age or birthweight between these groups. The funisitis (+) group had a significantly higher ventilator setting (inspired O2 × mean airway pressure) at Day 28 than the funisitis (-) group. In the TAF, the concentrations of IL-1β were significantly higher in the funisitis (+) group than in the funisitis (-) group, as were the concentrations of neutrophil elastase. The concentrations of EDA + FN were significantly lower in the funisitis (+) group than in the funisitis (-) group. Decreased EDA + FN in TAF might be one of the risk factors leading to respiratory distress in extremely premature infants with funisitis. Pediatr Pulmonol. © 2013 Wiley Periodicals, Inc.Pediatric Pulmonology 10/2013; 49(9). · 2.38 Impact Factor
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ABSTRACT: Rationale. Hyperoxia exposure to developing lungs-critical in the pathogenesis of bronchopulmonary dysplasia-may augment lung inflammation by inhibiting anti-inflammatory mediators in alveolar macrophages. Objective. We sought to determine the O2-induced effects on the polarization of macrophages and the role of anti-inflammatory BRP-39 in macrophage phenotype and neonatal lung injury. Methods. We used RAW264.7, peritoneal, and bone marrow derived macrophages for polarization (M1/M2) studies. For in vivo studies, wild-type (WT) and BRP-39(-/-) mice received continuous exposure to 21% O2 (control mice) or 100% O2 from postnatal (PN) 1 to PN7 days, along with intranasal lipopolysaccharide (LPS) administered on alternate days (PN2, -4, and -6). Lung histology, bronchoalveolar lavage (BAL) cell counts, BAL protein, and cytokines measurements were performed. Measurements and Main Results. Hyperoxia differentially contributed to macrophage polarization by enhancing LPS induced M1 and inhibiting interleukin-4 induced M2 phenotype. BRP-39 absence led to further enhancement of the hyperoxia and LPS induced M1 phenotype. In addition, BRP-39(-/-) mice were significantly more sensitive to LPS plus hyperoxia induced lung injury and mortality compared to WT mice. Conclusions. These findings collectively indicate that BRP-39 is involved in repressing the M1 proinflammatory phenotype in hyperoxia, thereby deactivating inflammatory responses in macrophages and preventing neonatal lung injury.Mediators of Inflammation 01/2013; 2013:457189. · 2.42 Impact Factor