Pro- and anti-inflammatory responses in respiratory syncytial virus bronchiolitis (original) (raw)
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Archives of Disease in Childhood - Fetal and Neonatal Edition, 1997
Aim-To investigate if early changes in concentrations of proinflammatory cytokines in tracheobronchial aspirate fluid (TAF) from preterm infants could be used to detect infants at risk of chronic lung disease (CLD) and help in the selection of patients for early steroid treatment. Methods-Twenty eight preterm infants less than 34 weeks of gestation (median 26 weeks) were intubated and daily measurements of TAF concentrations of tumour necrosis factor (TNF) and the interleukins IL-1 , IL-6, and IL-8 were made, using enzyme immunoassay techniques. Results-Seventeen of the infants developed CLD. The infants who developed CLD had significantly increased concentrations of TNF , IL-1ß, IL-6 on days 2 and 3. TNF , IL-6, and IL-8 concentrations were significantly related to gestational age and duration of supplemental oxygen; TNF , IL-6, and IL-8 concentrations also correlated with length of time on the ventilator. Conclusion-These data indicate that tracheobronchial aspirate fluid cytokine concentrations may be used as a predictor of subsequent CLD and may help select a group of preterm infants at high risk of developing CLD for early treatment.
Archives of Gynecology and Obstetrics, 2014
Purpose Intrauterine infection may induce the fetal inflammatory response syndrome (FIRS) and may cause cerebral palsy and bronchopulmonary dysplasia in newborns. The aim of the study was to evaluate the importance of FIRS for the early and later adaptation of preterms. Methods Hundred and fifty-eight preterm infants, born at 22-34 weeks of gestation, were investigated at Vilnius University Children hospital in [2007][2008][2009]. The data were evaluated at the first week after birth and at 36-37 weeks of post conceptual age. The levels of IL-6, tTNF-a (total), tVEGF-A (total), aTNF-a (active) and aVEGF-A (active) were determined. Results Correlation between IL-6 and tTNF-a from umbilical blood and the degree of respiratory distress syndrome (RDS) was found (p\0.001). The concentration of tTNF-a [345 pg/ml and IL-6 [12.7 pg/ml was determined allowing to predict the lethal outcome.
Children
Prematurity comes with a varying range of complications, implying a high prevalence of complications and mortality and depending on the severity of prematurity and the sustained inflammation among these infants, which recently sparked an important scientific interest. The primary objective of this prospective study was to establish the degree of inflammation in very (VPIs) and extremely preterm infants (EPIs) in association with the histology findings of the umbilical cord (UC), while the secondary objective was to study the inflammatory markers in the neonates’ blood as predictors of fetal inflammatory response (FIR). A total of thirty neonates were analyzed, ten of them being born extremely premature (<28 weeks of gestation) and twenty very premature (28–32 weeks of gestation). The EPIs had considerably higher levels of IL-6 at birth than VPIs (638.2 pg/mL vs. 151.1 pg/mL). The CRP levels at delivery did not vary substantially across groups; however, after days, the EPIs had si...
Inflammatory cytokines in newborn infants
Mediators of Inflammation, 1998
Serum levels of IL-1β, IL-6 and TNF-α were measured in 48 healthy, termed neonates on the 1st (N1), 5th (N5) and 40th (N40) day after birth, compared with those in maternal serum (MS), umbilical cord (UC) and adult controls. Cytokine values in N1 and N5 were significantly elevated, than those in UC and in controls(p<0.0001). IL-1β and IL-6 declined significantly from N1 to N40(p<0.0001), while TNF-α increased significantly from N1 to N5 and declined thereafter. MS∞IL-1β and IL-6, but not MS∞TNF-α, were significantly higher than those of controls(p<0.0001). IL-1β values depended on the mode of delivery. In conclusion, the increased concentrations of IL-1 β, IL-6 and TNF-α during the perinatal period might suggest their involvement in an inflammation like process during normal parturition, and reflect also a newborn immune response to the stress of delivery and environmental changes.
Modulation of pro- and anti-inflammatory cytokine production in very preterm infants
Cytokine, 2003
Background: In premature infants, outcome of infection-associated complications is heterogeneous despite advances in antibiotic treatment and diagnosis. Information on the immune response in preterm infants is limited. Immune modulatory strategies require detailed analysis of mediators and their kinetics. Objective: To determine the kinetics of IL-1b, TNFa, IL-6, IL-8, IL-10, cINF and G-CSF in preterm and term infants in an ex vivo cord blood culture (CBC) endotoxin model. Design and methods: Cord blood of 25 infants was obtained immediately after birth from the fetal side of the placenta and incubated in culture medium (RPMI 1640) in the presence or absence of 500 pg/ml lipopolysaccharide (LPS) for 48 h. TNFa, IL-1b, IL-6 and IL-8 were measured by sequential immunometric assay (IMMULITE Ò , DPC Biermann, Germany); IL-10 (Milenia Biotec, Bad Nauheim, Germany), cINF (Diaclone, Besancon, France) and G-CSF (R & D Systems, Wiesbaden, Germany) were determined by ELISA in supernatants at 0, 4, 8, 12, 24 and 48 h. Infants were stratified into three gestational age groups (32 weeks, 33-36 weeks, !37 weeks). Variations between the groups were first analyzed for significance by Kruskal-Wallis test and pairs were compared by Mann-Whitney-U test. Effects of gestational age, leucocyte count, hematocrit and frequency of antenatal steroid exposure were tested by linear regression analysis. To correct a possible impact of variable, WBC count, cytokine levels were adjusted according to individual leucocyte numbers. Results: LPS-stimulated maximum levels of IL-6, IL-1b,TNFa and G-CSF in CBC were significantly lower in very preterm infants compared to more advanced gestational age groups. After adjusting the cytokine levels for 10 5 leucocytes, a significant effect of gestational age on IL-6 and G-CSF production ðp , 0:05Þ was detected. A non-significant trend towards reduced cytokine levels was observed following multiple antenatal steroid exposures. IL-10 : TNFa ratio increased in very preterm neonates when compared with the advanced gestational age, although the increase was not significant. Conclusions: Pro-inflammatory cytokine activity in CBC correlates with gestational age, whereas IL-10 does not. Although ex vivo synthesis of IL-1b, TNFa, IL-6, G-CSF in CBC depends in part on leucocyte numbers, IL-6 and G-CSF synthesis appeared to be related to immaturity. Non-significant effects of multiple antenatal steroid exposure and increased IL-10 : TNFa ratio in preterm neonates, observed in a small sample size, warrant further investigation.
Journal of Perinatal Medicine, 2010
Aims: To evaluate the C-reactive protein (CRP) and interleukin-6 (IL-6) as diagnostic tools for early onset infection in preterm infants with early respiratory distress (RD). Methods: CRP and IL-6 were quantified at identification of RD and 24 h after in 186 newborns. Effects of maternal hypertension, mode of delivery, Apgar score, birth weight, gestational age, mechanical ventilation, being small for gestational age (SGA), and the presence of infection were analyzed. Results: Forty-four infants were classified as infected, 42 as possibly infected, and 100 as uninfected. Serum levels of IL-6 (0 h), CRP (0 h), and CRP (24 h), but not IL-6 (24 h) were significantly higher in infected infants compared to the remaining groups. The best test for identification of infection was the combination of IL-6 (0 h) 36 pg/dL and/or CRP (24 h) 0.6 mg/dL, which yielded 93% sensitivity and 37% specificity. The presence of infection and vaginal delivery independently increased IL-6 (0 h), CRP (0 h) and CRP (24 h) levels. Being SGA also increased the CRP (24 h) levels. IL-6 (24 h) was independently increased by mechanical ventilation. Conclusions: The combination of IL-6 (0 h) and/or CRP (24 h) is helpful for excluding early onset infection in preterm infants with RD but the poor specificity limits its potential benefit as a diagnostic tool.
Interleukin-6andinterleukin-8 as predictors of chronic lungdisease in premature infant
2015
Background:Improved survival from advances in neonatal care has resulted inan increased number of infants at risk for chronic lung disease (CLD). Pro-inflammatory cytokines such asinterleukins (IL)-6 and (IL)-8 play an importantrole in the inflammatory response to neonatal airway injury.In order to predict the late-development of CLD, cytokines in the blood samples were assessed in this study. Materials and Methods:IL6 and IL8 were measured in 45infants developing CLD in blood samples obtainedat 24 hours, 72 hoursand 1 week ofage. The normal range was established in blood samples of 59 consecutivehealthy pre-term infants. Cytokineconcentrations were quantified in duplicate using commerciallyavailable sandwich ELISA kits. Results:High initial levels of IL6 and IL8(first 24 h postnatal age) obtained in infantsdeveloping CLDindicate that this cytokines are not only markers but also initiators of inflammatory reaction. A persistent significant elevation of IL8 concentration in CLDgroup ...
Fetal and early neonatal interleukin-6 response
Cytokine, 2015
In 1998, a systemic fetal cytokine response, defined as a plasma interleukin-6 (IL-6) value above 11pg/mL, was reported to be a major independent risk factor for the subsequent development of neonatal morbid events even after adjustments for gestational age and other confounders. Since then, the body of literature investigating the use of blood concentrations of IL-6 as a hallmark of the fetal inflammatory response syndrome (FIRS), a diagnostic marker of early-onset neonatal sepsis (EONS) and a risk predictor of white matter injury (WMI), has grown rapidly. In this article, we critically review: IL-6 biological functions; current evidence on the association between IL-6, preterm birth, FIRS and EONS; IL-6 reference intervals and dynamics in the early neonatal period; IL-6 response during the immediate postnatal period and perinatal confounders; accuracy and completeness of IL-6 diagnostic studies for EONS (according to the Standards for Reporting of Diagnostic Accuracy statement); a...
Systemic inflammation associated with mechanical ventilation among extremely preterm infants
Cytokine, 2013
Little evidence is available to document that mechanical ventilation is an antecedent of systemic inflammation in preterm humans. We obtained blood on postnatal day 14 from 726 infants born before the 28th week of gestation and measured the concentrations of 25 inflammation-related proteins. We created multivariable models to assess the relationship between duration of ventilation and protein concentrations in the top quartile. Compared to newborns ventilated for fewer than 7 days (N=247), those ventilated for 14 days (N=330) were more likely to have elevated blood concentrations of pro-inflammatory cytokines (IL-1β, TNF-α), chemokines (IL-8, MCP-1), an adhesion molecule (ICAM-1), and a matrix metalloprotease (MMP-9), and less likely to have elevated blood concentrations of two chemokines (RANTES, MIP-1β), a matrix metalloproteinase (MMP-1), and a growth factor (VEGF). Newborns ventilated for 7-13 days (N=149) had systemic inflammation that approximated the pattern of newborns ventilated for 14 days. These relationships were not confounded by chorioamnionitis or antenatal corticosteroid exposure, and were not altered appreciably among infants with and without bacteremia. These findings suggest that two weeks of ventilation are more likely than shorter durations of ventilation