interleukin-8 and Respiratory-Distress-Syndrome--Newborn

Congenital heart disease (CHD) after cardiopulmonary bypass can cause systemic inflammation, and its degree is closely related to the incidence of acute respiratory distress syndrome (ARDS). The purpose of this study was to determine the effectiveness of high-frequency oscillatory ventilation (HFOV) combined with volume guarantee (VG) in reducing systemic inflammation in infants with ARDS after cardiopulmonary bypass for congenital heart surgery.. A randomized controlled trial.. Single-center study in a tertiary teaching hospital.. A total of 58 infants with ARDS after congenital heart surgery were eligible and were randomized to the HFOV (n = 29) or the HFOV-VG (n = 29) between January 2020 and January 2021.. Tracheal aspirate samples for the measurement of interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) were obtained on days one, two, and three of HFOV or HFOV-VG ventilation.. The authors found a significantly increasing trend in the HFOV group mean values of IL-6, IL-8, and TNF-α (p < 0.05 on days two and three v day one), and IL-6, IL-8, and TNF-α levels were significantly higher on day three in the HFOV group versus the HFOV+VG group (p < 0.05). In addition, the incidences of hypocapnia and hypercapnia in infants supported with HFOV-VG were significantly lower (p < 0.05). Furthermore, the postoperative mechanical ventilation duration in the HFOV-VG group also was shorter than that in the HFOV group (p < 0.05).. Compared with HFOV alone, HFOV-VG reduced proinflammatory systemic reactions after congenital cardiac surgery, decreased the incidences of hypercapnia and hypocapnia, and shortened the postoperative mechanical ventilation duration.

Topics: High-Frequency Ventilation; Humans; Hypercapnia; Hypocapnia; Infant; Infant, Newborn; Infant, Premature; Inflammation; Interleukin-6; Interleukin-8; Lung; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Tumor Necrosis Factor-alpha

The aim of this study was to determine the effects of inhaled NO with different oxygen concentrations on the inflammatory cascade in newborns with hypoxic respiratory failure secondary to persistent pulmonary hypertension.. 60 newborns received iNO and 30 of them received an initial oxygen concentration of 45% (group 1), while the other 30 newborns received an initial oxygen concentration of 80% (group 2). The levels of inflammatory cytokines (IL-6, IL-8, TNF-α) were measured. The clinical outcome was also recorded.. The findings show that interleukin concentrations (IL-6, IL-8, TNF-α) were significantly decreased between 0 and 72 hours (p < 0.01) in the newborns exposed to initial oxygen concentration of 45% and significantly increased in the other group.. When inhaled, NO was co-administered with concentration of O(2) <45%, anti-inflammatory responses occurred, in accord with evidence in the published literature. The benefits of iNO on the clinical outcome in the current study demonstrate that inhaled NO in both groups was associated with improved short-term oxygenation.

Topics: Administration, Inhalation; Dose-Response Relationship, Drug; Female; Humans; Infant, Newborn; Interleukin-6; Interleukin-8; Male; Nitric Oxide; Oxidative Stress; Oxygen; Persistent Fetal Circulation Syndrome; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; Tumor Necrosis Factor-alpha

The objective of this study was to compare the pulmonary inflammatory response of premature infants with respiratory distress following instillation of one of two commonly available surfactant preparations.. This was a prospective, randomized investigation of preterm infants who were less than 30 weeks of gestational age, weighed less than 1 kg at birth, and who qualified to receive surfactant. Infants with multiple congenital anomalies or whose mothers were taking anti-inflammatory medications were ineligible. Tracheal aspirates (TAs) were collected on days 1, 3, 5, and 7 and airway cytokines from TAs were assayed for interleukin (IL)-8 and IL-6.. Infants were evenly matched by gestation (26+/-2 days and 26+/-1 days [mean+/-SD], Surfactant A and B, respectively) and birth weight (730+/-141 g and 732+/-167 g). TA cytokine levels were not different between or within groups. Ventilator requirements and clinical outcomes were similar between the two groups.. The postnatal airway inflammatory response observed in preterm infants is not altered by the instillation of either surfactant preparation.

Topics: Cytokines; Female; Humans; Infant, Newborn; Infant, Premature; Interleukin-6; Interleukin-8; Male; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn; Respiratory Physiological Phenomena; Trachea

Ventilation with an inappropriate tidal volume (Vt) triggers lung inflammation, an important predisposing factor of bronchopulmonary dysplasia. It still remains uncertain what the appropriate starting target Vt should be during the acute phase of respiratory distress syndrome (RDS). Our aim was to evaluate lung inflammation in preterm infants undergoing synchronized intermittent positive-pressure ventilation (SIPPV) with two different tidal volumes Vt during the acute phase of RDS. Thirty preterm infants (gestational age, 25-32 weeks) with acute RDS were randomly assigned to be ventilated with Vt = 5 ml/kg (n = 15) or Vt = 3 ml/kg (n = 15). Proinflammatory cytokines (interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor (TNF)-alpha) were determined in the tracheal aspirate on days 1, 3, and 7 of life. IL-8 and TNF-alpha levels collected on day 7 were significantly higher (P < 0.05), and mechanical ventilation lasted longer in the group with Vt = 3 ml/kg (16.8 +/- 4 vs. 9.2 +/- 4 days; P = 0.05). In conclusion, our data show significantly higher lung inflammation in preterm infants ventilated with Vt = 3 ml/kg, suggesting a role for Vt = 5 ml/kg in reducing both inflammatory response during the acute phase of RDS and the length of ventilation. Whether the use of this starting Vt prevents bronchopulmonary dysplasia requires further study.

Topics: Humans; Infant, Newborn; Infant, Premature; Interleukin-8; Lung; Positive-Pressure Respiration; Respiratory Distress Syndrome, Newborn; Tidal Volume; Time Factors; Trachea; Tumor Necrosis Factor-alpha

Reactive oxygen species play an important role in the pathogenesis of respiratory distress syndrome and its complications. This study was conducted to determine if treatment with the antioxidant melatonin would influence interleukin-6, interleukin-8, tumor necrosis factor alpha, and nitrite/nitrate levels in newborns with grade III or IV respiratory distress syndrome (radiographically confirmed) diagnosed within the first 6 hours of life. Prior to treatment, a blood sample was collected from the umbilical cord or a peripheral vein of each newborn. Second, third, and fourth blood samples were collected at 24 hours, 72 hours, and 7 days, respectively, after beginning treatment with melatonin or placebo. Compared with the melatonin-treated respiratory distress syndrome newborns, in the untreated infants the concentrations of interleukin-6, interleukin-8, and tumor necrosis factor alpha were significantly higher at 24 hours, 72 hours, and at 7 days after onset of the study. in addition, nitrite/nitrate levels at all time points were higher in the untreated respiratory distress syndrome newborns than in the melatonin-treated babies. Following melatonin administration, nitrite/nitrate levels decreased significantly, whereas they remained high and increased further in the respiratory distress syndrome infants not given melatonin.

Topics: Antioxidants; Humans; Infant, Newborn; Infant, Premature; Interleukin-6; Interleukin-8; Melatonin; Nitrates; Nitrites; Oxidative Stress; Respiratory Distress Syndrome, Newborn; Statistics, Nonparametric; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha

Pro-inflammatory cytokines such as IL-8 play an important role in the inflammatory response to neonatal airway injury. Difficulty in detecting counter-regulatory cytokines such as IL-10 in lavage fluid from preterm infants led to the suggestion that its deficit may be a factor in the etiology of chronic lung disease of prematurity (CLD). The aim of the study was to determine IL-8 and IL-10 concentrations in lavage fluid from preterm infants ventilated for respiratory distress syndrome. Fifty infants <30 wk gestation were studied who had been randomized to receive a natural or synthetic surfactant. Lavage samples were collected daily for the first week and twice weekly thereafter. Samples were immediately centrifuged and stored at -70 degrees C. Cytokine concentrations were quantified in duplicate using commercially available sandwich ELISA kits. Lavage IL-10 concentration, at a minimum initially, rose significant over the first five postnatal days (p = 0.009). In the same samples, lavage IL-8 concentrations rose significantly over the first postnatal week (p < 0.001), the rise preceding that of IL-10. Infants dying or developing CLD had a significant early rise in both cytokine concentrations. Compared with infants developing CLD, lavage IL-10 concentrations were significantly higher on d 1 among those not developing CLD but significantly lower on d 4 (p < 0.05). To conclude, IL-10 is detectable in lavage fluid from ventilated preterm infants and its concentrations rise significantly over the first five postnatal days. In the same samples, IL-8 concentration also rises and this increase precedes the rise in IL-10.

Topics: Bronchoalveolar Lavage Fluid; Chronic Disease; Humans; Infant, Newborn; Infant, Premature; Interleukin-10; Interleukin-8; Lung Diseases; Prognosis; Pulmonary Surfactants; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; Time Factors

To measure plasma levels of vascular endothelial growth factor (VEGF) and several cytokines (Interleukin [IL]-6 IL-8, IL-10) during the first week of life to examine the relationship between protein expression and likelihood of developing respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD).. Levels of IL-6, IL-8, IL-10, and VEGF were measured from plasma obtained from preterm patients during the first week of life. Newborns were recruited from a single center between April 2009 and April 2019. Criteria for the study included being inborn, birth weight of less than 1500 grams, and a gestational age of less than 32 weeks at birth.. The development of RDS in preterm newborns was associated with lower levels of VEGF during the first week of life. Higher plasma levels of IL-6 and IL-8 plasma were associated with an increased likelihood and increased severity of BPD at 36 weeks postmenstrual age. In contrast, plasma levels of VEGF, IL-6, IL-8, and IL-10 obtained during the first week of life were not associated with respiratory symptoms and acute care use in young children with BPD in the outpatient setting.. During the first week of life, lower plasma levels of VEGF was associated with the diagnosis of RDS in preterm infants. Preterm infants with higher levels of IL-6 and IL-8 during the first week of life were also more likely to be diagnosed with BPD. These biomarkers may help to predict respiratory morbidities in preterm newborns during their initial hospitalization.

Topics: Biomarkers; Bronchopulmonary Dysplasia; Cytokines; Female; Humans; Infant; Infant, Newborn; Infant, Premature; Interleukin-10; Interleukin-6; Interleukin-8; Pregnancy; Respiratory Distress Syndrome, Newborn; Vascular Endothelial Growth Factor A

We studied the relationship between ultrasound-assessed lung aeration and inflammation in a particular population of ventilated preterm neonates with mild-to-moderate lung inflammation and no congenital heart defect. Lung aeration estimated by a semiquantitative lung ultrasound score significantly correlated with several inflammatory markers both at cellular (neutrophil count in bronchoalveolar lavage: ρ = 0.400, p = 0.018) and molecular level (total proteins: ρ = 0.524, p = 0.021; interleukine-8: ρ = 0.523, p = 0.021; granulocytes-macrophages colony stimulating factor: ρ = 0.493, p = 0.020; all measured in bronchoalveolar lavage and expressed as epithelial lining fluid concentrations). Lung ultrasound might detect changes in lung aeration attributable to mild-to-moderate local inflammation if cardiogenic lung edema is excluded. Thus, it is possible to describe some levels of lung inflammation with semiquantitative lung ultrasound.

Topics: Biomarkers; Bronchoalveolar Lavage; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Infant, Newborn; Infant, Premature; Interleukin-8; Leukocyte Count; Lung; Male; Neutrophils; Prospective Studies; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; Ultrasonography

Topics: Child; Humans; Interleukin-8; Prospective Studies; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Respiratory Insufficiency

Factors influencing intraamniotic adiponectin levels and their functional significance remain incompletely elucidated. We prospectively measured adiponectin in amniotic fluid and identified its associations with maternal parameters, mediators in amniotic fluid and pregnancy outcomes.. Mid-trimester amniotic fluid from 571 women was tested for adiponectin, interleukin (IL)-6, IL-8 and α-amylase by enzyme-linked immunosorbant assay (ELISA), after which clinical data were obtained. Correlations between adiponectin and clinical or laboratory variables were analyzed by the Kruskal-Wallis, Mann-Whitney and Spearman rank correlation tests.. As compared to median levels in 462 women with a term delivery (7.8 ng/mL), adiponectin was elevated in 14 women who subsequently developed preterm premature rupture of membranes (pPROM) (17.3 ng/mL) and 24 women with an iatrogenic preterm birth (IPTB) (13.9 ng/mL) (P=0.0003), but not in 30 women who subsequently had a spontaneous preterm birth with intact membranes (8.1 ng/mL) (P>0.05). Median adiponectin was also elevated in 13 women whose babies developed fetal growth restriction (FGR) (20.6 ng/mL) (P=0.0055) and in 22 women whose babies had respiratory distress syndrome (RDS) (23.0 ng/mL) (P<0.0001). The adiponectin concentration was positively correlated with amylase (P=0.0089) and inversely correlated with maternal body mass index (P=0.0045).. Adiponectin is a component of mid-trimester amniotic fluid and its concentration varies with maternal body mass index and subsequent development of pPROM, IPTB, FGR and RDS.

Topics: Adiponectin; Adult; alpha-Amylases; Amniotic Fluid; Body Mass Index; Female; Humans; Infant, Newborn; Interleukin-6; Interleukin-8; Middle Aged; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnancy Trimester, Second; Prospective Studies; Respiratory Distress Syndrome, Newborn; Young Adult

New generation synthetic surfactants represent a promising alternative in the treatment of respiratory distress syndrome in preterm infants. CHF5633, a new generation reconstituted agent, has demonstrated biophysical effectiveness in vitro and in vivo. In accordance to several well-known surfactant preparations, we recently demonstrated anti-inflammatory effects on LPS-induced cytokine responses in human adult monocytes. The present study addressed pro- and anti-inflammatory effects of CHF5633 in human cord blood monocytes.. Purified neonatal CD14(+) cells, either native or simultaneously stimulated with E. coli LPS, were exposed to CHF5633. TNF-α, IL-1β, IL-8 and IL-10 as well as TLR2 and TLR4 expression were analyzed by means of real-time quantitative PCR and flow cytometry.. CHF5633 did not induce pro-inflammation in native human neonatal monocytes and did not aggravate LPS-induced cytokine responses. Exposure to CHF5633 led to a significant decrease in LPS-induced intracellular TNF-α protein expression, and significantly suppressed LPS-induced mRNA and intracellular protein expression of IL-1β. CHF5633 incubation did not affect cell viability, indicating that the suppressive activity was not due to toxic effects on neonatal monocytes. LPS-induced IL-8, IL-10, TLR2 and TLR4 expression were unaffected.. Our data confirm that CHF5633 does not exert unintended pro-apoptotic and pro-inflammatory effects in human neonatal monocytes. CHF5633 rather suppressed LPS-induced TNF-α and IL-1β cytokine responses. Our data add to previous work and may indicate anti-inflammatory features of CHF5633 on LPS-induced monocyte cytokine responses.

Topics: Cytokines; Fetal Blood; Flow Cytometry; Humans; Infant, Newborn; Interleukin-10; Interleukin-1beta; Interleukin-8; Lipopolysaccharide Receptors; Lipopolysaccharides; Monocytes; Peptide Fragments; Phosphatidylcholines; Pulmonary Surfactant-Associated Protein B; Pulmonary Surfactant-Associated Protein C; Real-Time Polymerase Chain Reaction; Respiratory Distress Syndrome, Newborn; Toll-Like Receptor 2; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

We studied the role of ante- and post-natal infection in the development of chronic lung disease (CLD) of prematurity. 192 newborn infants (61 term and 131 pre-term of <34 weeks gestation: 88 with respiratory distress syndrome, 35 developed CLD and eight died) were recruited. 16S ribosomal RNA (rRNA) genes were identified by PCR of DNA isolated from 840 gastric and lung fluid samples. Ureaplasma spp. were also cultured. Presence of 16S rRNA genes (OR 1.6, 95% CI 1.2-2.2) and Ureaplasma spp. (OR 3.6, 95% CI 1.7-7.7) was significantly associated with the development of CLD. This association remained if the 16S rRNA genes and Ureaplasma spp. were first identified within the first 3 days of life (OR 2.4 (95% CI 1.4-4.1) and 3.8 (95% CI 1.4-10.0), respectively) or if first identified after 3 days of age (OR 1.7 (95% CI 1.1-2.8) and OR 5.1 (95% CI 1.3-19.8), respectively). Peak lung fluid interleukin (IL)-6 and IL-8 were significantly associated with presence of microbes (p<0.0001 and p=0.0001, respectively) and development of CLD (p=0.003 and 0.001, respectively). Both early and late microbial presence in neonatal lung fluid samples was significantly associated with the development of CLD suggesting that both ante- and post-natal infection play a role in the development of CLD.

Topics: Chronic Disease; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Interleukin-6; Interleukin-8; Male; Respiratory Distress Syndrome, Newborn; RNA, Ribosomal, 16S; Ureaplasma Infections

The role of granulocyte-specific S100A12, a marker for inflammatory disorders, in newborn lung disease is unknown. We compared postnatal blood S100A12 concentrations against respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD).. Blood samples from 92 newborns were collected on admission, 12 h, day 1, day 3-4 and day 7, and analysed for S100A12. IL-8 and IL-6 were assayed in 52 infants.. Infants with RDS were significantly more premature (median 27 vs. 34 weeks), more likely to receive antenatal corticosteroids (84% vs. 26%) and have lower neutrophil counts (median 2.4 vs. 3.8 × 10(9) /L) at admission. S100A12 levels peaked during the first day and were significantly lower in preterm infants with RDS compared to those without (median 250 vs. 616 ng/mL at 12 h, 281 vs. 828 ng/mL day 1, respectively). S100A12 levels were low among the 35 very preterm infants (24-29 week gestation) regardless of the presence of BPD (285 vs. 288 ng/mL on day 1). In comparison, IL-8 and IL-6 levels were not different between groups.. Plasma S100A12 is low in infants with RDS, possibly because of gestationally related differences in neutrophil response or to the effects of antenatal corticosteroids. It is therefore not a useful marker of BPD development.

Topics: Biomarkers; Bronchopulmonary Dysplasia; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Interleukin-6; Interleukin-8; Leukocyte Count; Logistic Models; Neutrophils; Respiratory Distress Syndrome, Newborn; S100 Proteins; S100A12 Protein

Natural surfactant combined with beclomethasone decreases pulmonary oxidative stress in preterm lambs with respiratory distress syndrome (RDS).. To test the hypothesis that this occurs through a decrease in pulmonary inflammation.. Preterm lambs received 200 mg/kg of natural surfactant or 200 mg/kg of natural surfactant combined with 400 or 800 μg/kg of beclomethasone. Interleukin 8 (IL-8) and macrophage migration inhibitory factor (MIF) were assayed in bronchial aspirate samples and lung mechanics were evaluated.. IL-8 increased in all the groups, but the increase was lower in the groups treated with surfactant plus 400 and 800 μg/kg of beclomethasone. MIF decreased in the surfactant group, did not vary in the surfactant plus 400 μg/kg beclomethasone group, and decreased in the surfactant plus 800 μg/kg beclomethasone group. MIF concentration was higher in the surfactant plus 800 μg/kg beclomethasone group than in the other groups.. Natural surfactant combined with beclomethasone at 800 μg/kg is effective in reducing lung inflammation in an animal model of RDS, thus explaining the associated decrease in lung oxidative stress. The increase in MIF in animals treated with surfactant plus 800 μg/kg of beclomethasone might be an important maturative and protective factor for neonatal lungs.

Topics: Animals; Animals, Newborn; Anti-Inflammatory Agents; Beclomethasone; Disease Models, Animal; Female; Humans; Infant, Newborn; Interleukin-8; Macrophage Migration-Inhibitory Factors; Oxidative Stress; Pneumonia; Pregnancy; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn; Sheep

The aim of the present study was to investigate the association of chronic lung disease (CLD), neonatal Ureaplasma colonization, and interleukin-8 (IL-8) level of cord blood in preterm infants.. In 77 infants of <32 weeks gestation, the relationship between IL-8 level of cord blood, neonatal colonization of Ureaplasma, histological chorioamnionitis (CAM), and development of CLD was studied.. Five infants died and 29 infants developed CLD. The CLD group had significantly lower gestation (mean ± SD: 26.6 ± 1.8 weeks) compared with the infants without CLD (28.9 ± 1.9 weeks, P < 0.0001). Logistic analysis showed that the development of CLD was associated with gestational age (odds ratio [OR], 0.5; 95% confidence interval (CI): 0.4-0.8) and Ureaplasma colonization (OR, 4.1; 95%CI: 1.2-14.4). Ureaplasma colonization was also associated with CAM (OR, 6.5; 95%CI: 1.8-23.5), absence of respiratory distress syndrome (OR, 6.2; 95%CI: 1.3-30.5), and development of CLD (OR, 4.0; 95%CI: 1.1-15.3). Elevated cord blood IL-8 ≥100 pg/mL was associated with female sex and the isolation of microorganisms (OR, 49.4; 95%CI: 4.6-525).. The development of CLD defined by oxygen requirement at 36 weeks was associated with neonatal Ureaplasma colonization but not with IL-8 level of cord blood. Elevated cord blood IL-8 was associated with neonatal microorganisms isolation.

Topics: Analysis of Variance; Biomarkers; Chronic Disease; Cohort Studies; Confidence Intervals; Female; Fetal Blood; Gestational Age; Humans; Incidence; Infant, Newborn; Infant, Premature; Intensive Care Units, Neonatal; Interleukin-8; Lung Diseases; Male; Multivariate Analysis; Odds Ratio; Pregnancy; Prognosis; Prospective Studies; Respiratory Distress Syndrome, Newborn; Survival Rate; Ureaplasma; Ureaplasma Infections

Recent literature suggests hypothermia may protect against lung injury. We evaluated body temperature as a variable in lung inflammation due to oxygenation and mechanical ventilation following delivery of near-term lambs.. Twin fetuses were randomized prior to delivery at 140 d GA (term 150 d): unventilated controls, normothermic ventilated with room air, normothermic ventilated with 100% oxygen, low temperature ventilated (target 35 degrees C) with 100% oxygen, and high temperature (target 40 degrees C) with 100% oxygen. Lambs were intubated for gentle mechanical ventilation (tidal volume 7-8ml/kg). Temperature targeting was with radiant warmers and plastic wrap for normothermia, with heat lamps for hyperthermia, and with ice packs for hypothermia. Lambs were euthanized after 2h mechanical ventilation. Post-mortem, bronchoalveolar lavage fluid and lung tissue samples were evaluated for inflammatory responses by measuring inflammatory cell counts, protein, myeloperoxidase, protein carbonyl, and pro-inflammatory cytokine mRNA.. Target temperatures were achieved by 30min of age and tightly maintained for the 2h study. There were no differences in physiologic variables among groups except those directly resulting from study protocol-PaO2 from air vs. 100% oxygen and body temperature. Indicators of inflammation increased similarly in all ventilated groups compared to unventilated controls.. Moderate hyperthermia or hypothermia did not affect lung injury responses to the initiation of ventilation at birth in near-term lambs.

Topics: Animals; Body Temperature; Bronchoalveolar Lavage Fluid; Cell Count; Disease Models, Animal; Fetus; Humans; Hyperthermia, Induced; Hypothermia; Hypothermia, Induced; Infant, Newborn; Inflammation; Interleukin-1beta; Interleukin-6; Interleukin-8; Lung; Random Allocation; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; Sheep; Treatment Outcome; Twins

Respiratory distress syndrome (RDS) incidence is increased in infants of preeclamptic mothers with hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. RDS and HELLP syndrome have been associated with oxidative stress and inflammatory processes.. We hypothesize that end-tidal carbon monoxide corrected for inhaled CO (ETCOc), malondialdehyde (MDA) (markers of oxidative stress) and proinflammatory cytokine (IL-6, IL-8) production are higher in infants of preeclamptic mothers with HELLP syndrome than in those of preeclamptic mothers without HELLP syndrome.. Prospective study of 36 infants of preeclamptic mothers (GA <32 weeks) admitted to the Neonatal Intensive Care Unit. ETCOc was measured at 0-12, 48-72 and 168 h postnatally using the CO-Stattrade mark End-Tidal Breath Analyzer. Simultaneously, blood was sampled for MDA, IL-8 and IL-6.. At 0-12 h, ETCOc, MDA and IL-8 values (median[range]) were significantly higher in HELLP infants than in infants from preeclamptic mothers without HELLP (ETCOc 2.2 [1.5-3.9] vs. 1.8 [0.5-2.9] ppm; MDA 2.3 [1.3-4.1] vs. 1.5 [0.4-3.1] mumol/l; IL-8 145 [24-606] vs. 62 [26-397] pg/ml; all p <0.05). MDA remained significantly higher during the first 168 h of life (2.3 [0.8-5.8] vs. 1.1 [0.8-3.7] mumol/l, p = 0.02).. Oxidative stress and proinflammatory cytokine levels are increased in infants of preeclamptic mothers with HELLP syndrome. These processes may cause inactivation of surfactant explaining the increased RDS incidence in these infants.

Topics: Adult; Apgar Score; Breath Tests; Female; Fetal Blood; HELLP Syndrome; Humans; Infant, Newborn; Infant, Premature; Interleukin-6; Interleukin-8; Interleukins; Male; Oxidative Stress; Pre-Eclampsia; Pregnancy; Prospective Studies; Respiratory Distress Syndrome, Newborn

We investigated the relation between perinatal endotracheal colonization, the associated cytokine response and respiratory outcome in ventilated preterm neonates. Between September 1999 and March 2002, a cohort of 141 neonates with a gestational age <31 weeks requiring ventilation directly after birth, were followed prospectively. All were admitted to the Neonatal Intensive Care Unit, University Hospital of Antwerp, Belgium. A tracheal aspirate (TA) sample was collected soon after birth and was processed for microbiological examination, leukocyte count, and cytokine analysis (interleukins [IL] IL-1beta, IL-6, CXCL8 (formerly called IL-8), IL-10, IL-12p70 and tumor necrosis factor alpha [TNF-alpha]). Together with the prospectively registered patient's comorbidities and severity of disease, these inflammatory parameters were analyzed in a multivariate Cox proportional hazards model with time of extubation and duration of oxygen therapy as main outcome measures. Of the 141 patients included, 31 (22%) died before discharge from the unit and 37 (26%) had a positive TA culture. Independent predictors of duration of mechanical ventilation were: gestational age <28 weeks, degree of respiratory distress syndrome (RDS) at birth, significant patent ductus arteriosus (PDA), the SNAP-score, and high levels of CXCL8 (>4,153 pg/ml) in TA only in neonates with a gestational age <28 weeks. Variables associated with extended duration of oxygen therapy were gestational age <28 weeks, birth weight <1,000 g, degree of RDS at birth, and duration of mechanical ventilation.

Topics: Body Fluids; Bronchopulmonary Dysplasia; Cytokines; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Interleukin-8; Leukocyte Count; Prognosis; Prospective Studies; Respiratory Distress Syndrome, Newborn; Risk Factors; Trachea

We hypothesized that enriching surfactant with hyaluronan would restore lung function when tested in a premature animal model. Newborn piglets (85% gestation, term 112-114 days) were delivered by cesarean section, subjected to mechanical ventilation (tidal volume 6- 8 ml/kg) and randomly assigned to treatment with 50 or 100 mg/kg Curosurf (C50 and C100), 50 or 100 mg/kg Curosurf mixed with 2.5% HA (w/w, CH50 and CH100). A ventilated and not treated group (Cont) and a not treated and not ventilated group (Non) were included as controls. Six hours after treatment the lungs were removed and biochemical, biophysical, cytological and histological analyses were carried out. The CH100, CH50, C100 and C50 groups had variable but significantly improved alveolar phospholipid content, minimal surface tension, alveolar aeration and wet/dry lung weight ratios, but little histological evidence of lung injury. CH100, CH50 and C100 groups had the best effects in terms of oxygenation, lung compliance and histology and evidence of decreased inflammation (IL-8 and TNF-alpha mRNA expression). We conclude that HA added to 50 mg/kg Curosurf or use of 100 mg/kg Curosurf with or without HA provides the best effects in terms of lung function and reduction of inflammation.

Topics: Animals; Animals, Newborn; Anti-Inflammatory Agents; Biological Products; Disease Models, Animal; Humans; Hyaluronic Acid; Infant, Newborn; Interleukin-1; Interleukin-10; Interleukin-6; Interleukin-8; Lung; Malondialdehyde; Peroxidase; Phospholipids; Pulmonary Surfactant-Associated Protein A; Pulmonary Surfactant-Associated Protein B; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; RNA, Messenger; Swine; Tumor Necrosis Factor-alpha

Leukotriene-generated effects on microvascular integrity and polymorphonuclear leukocytes (PMNL) play a key role in the inflammatory process of the alveolar-capillary unit in neonatal acute respiratory distress syndrome. We asked if intrapulmonary application of MK886, a 5-lipoxygenase inhibitor, and the use of a porcine surfactant preparation (Curosurftrade mark) as a carrier substance would improve lung function in a neonatal piglet model of airway lavage. Anesthetized, mechanically ventilated newborn piglets (n = 19) underwent repeated airway lavage to induce acute lung injury. Piglets then received either surfactant alone (S, n = 6), or MK886 admixed with surfactant (S + MK, n = 7), or an air-bolus injection as control (C, n = 6). Measurements of gas exchange, lung function, extravascular lung water (EVLW), cell counts, and leukotriene B(4) (LTB(4)) concentrations in bronchoalveolar lavage fluid (BAL) were performed during 6 hr of mechanical ventilation. Arterial oxygen partial pressure (PaO(2)) (S, 13.8 +/- 4.2 kPa, vs. S + MK, 20 +/- 6.6; P < 0.05), functional residual capacity (S, 15.1 +/- 6.8 ml/kg, vs. S + MK, 18.8 +/- 3.7 ml/kg; P < 0.05), and EVLW (S, 29 +/- 14 ml/kg, vs. S + MK 24 +/- 4 ml/kg; P < 0.05) were significantly improved in the MK886 group. This clinical effect was linked with a decrease in LTB(4) concentration in BAL (S, 3.5 (1.9-5.4) pg/ml, vs. S + MK, 1.6 (0.7-4.7) pg/ml; P < 0.05) and an increase in IL-8 (S, 2,103 (852-4,243) pg/ml, vs. S + MK, 3,815 (940-26,187) pg/ml; P < 0.05). PMNL counts in BAL were reduced (S, 570 +/- 42 cells/ml, vs. 275 +/- 35 cells/ml; P < 0.05). In conclusion, intrapulmonary application of the 5-lipoxygenase inhibitor MK886 with surfactant as a carrier improves lung function by decreasing EVLW as the main response to LTB(4) reduction.

Topics: Animals; Animals, Newborn; Biological Products; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Female; Hemodynamics; Humans; Indoles; Infant, Newborn; Interleukin-8; Leukotriene B4; Lipoxygenase Inhibitors; Lung; Male; Phospholipids; Pulmonary Edema; Pulmonary Gas Exchange; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; Swine

To investigate whether or not peri/intraventricular hemorrhages (PIVHs) occurring in the first 12 hours of life (early PIVHs) are related to respiratory distress syndrome (RDS)-associated inflammatory factors in contrast to PIVHs developing after 12 hours of life (late PIVHs).. Blood samples obtained at 0 to 12 hours, 48 to 72 hours, and 168 hours of life were evaluated for determination of the proinflammatory cytokines interleukin (IL)-8 and IL-6, tumor necrosis factor (TNF)-alpha, and malondialdehyde (MDA) as measures of lipid peroxidation. Simultaneously, cranial ultrasonography was performed in 114 neonates under 32 weeks gestational age.. Out of the total study group of 114 neonates, 67 (59%) had RDS. Early PIVH occurred in 16 neonates, 14 of whom (88%) had RDS. Late PIVHs occurred in 12 neonates. Neonates with RDS had higher IL-8 and IL-6 levels at 0 to 12 hours (P < .0001; < .0001) and at 48 to 72 hours (P < .001; < .01) than those without RDS. Neonates with early PIVH had higher IL-8 (P < .02), IL-6 (P < .02), and MDA (P < .01) levels at 0 to 12 hours than those with late PIVH or no PIVH. Those with early PIVH had higher IL-8 levels at 48 to 72 hours than those without PIVH (P < .02). Multiple linear regression revealed an association between RDS/early PIVH and IL-8, IL-6, and MDA levels.. An RDS-associated increase in proinflammatory cytokine and MDA levels was associated with early PIVHs, but not with late PIVHs, suggesting a different etiopathogenesis in early versus late PIVHs.

Topics: Age Factors; Cerebral Hemorrhage; Cytokines; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Inflammation; Interleukin-6; Interleukin-8; Linear Models; Lipid Peroxidation; Malondialdehyde; Oxidative Stress; Respiratory Distress Syndrome, Newborn; Tumor Necrosis Factor-alpha; Ultrasonography

To evaluate standardized lung recruitment strategy during both high frequency oscillation (HFO) and volume-targeted conventional ventilation (CV+V) in spontaneously breathing piglets with surfactant washout on pathophysiologic and inflammatory responses.. Prospective animal study.. Research laboratory.. Twenty-four newborn piglets.. We compared pressure support and synchronized intermittent mandatory ventilation, both with targeted tidal volumes, (PSV+V, SIMV+V) to HFO. Animals underwent saline lavage to produce lung injury, received artificial surfactant and were randomized to one of the three treatment groups (each n=8). After injury and surfactant replacement, lung volumes were recruited in all groups using a standard protocol. Ventilation continued for 6 h.. Arterial and central venous pressures, heart rates, blood pressure and arterial blood gases were continuously monitored. At baseline, post lung injury and 6 h we collected serum and bronchoalveolar lavage samples for proinflammatory cytokines: IL 6, IL 8 and TNF-alpha, and performed static pressure-volume (P/V) curves. Lungs were fixed for morphometrics and histopathologic analysis. No physiologic differences were found. Analysis of P/V curves showed higher opening pressures after lung injury in the HFO group compared to the SIMV+V group ( p<0.05); no differences persisted after treatment. We saw no differences in change in proinflammatory cytokine levels. Histopathology and morphometrics were similar. Mean airway pressure (P(aw)) was highest in the HFO group compared to SIMV+V ( p<0.002).. Using a standardized lung recruitment strategy in spontaneously breathing animals, CV+V produced equivalent pathophysiologic outcomes without an increase in proinflammatory cytokines when compared to HFO.

Topics: Animals; Animals, Newborn; Hemodynamics; High-Frequency Ventilation; Humans; Infant, Newborn; Interleukin-6; Interleukin-8; Intermittent Positive-Pressure Ventilation; Lung; Prospective Studies; Random Allocation; Respiratory Distress Syndrome, Newborn; Respiratory Mechanics; Swine; Tumor Necrosis Factor-alpha

The study investigates the effectiveness of aerosol treatment on gas exchange and pulmonary inflammatory reaction using perfluorocarbons with different molecular structure and vapor pressure.. Experimental, prospective, randomized, controlled study.. Experimental laboratory at a university hospital.. Twenty anesthetized neonatal piglets assigned to four groups.. After establishment of lung injury by bronchoalveolar lavage, piglets either received aerosolized FC77 (n = 5), perfluorooctylbromide (n = 5), or FC43 (n = 5, 10 mL x kg(-1) x hr(-1) for 2 hrs) or intermittent mandatory ventilation (control, n = 5). Thereafter, animals were supported for another 6 hrs.. Pao2 significantly improved in the perfluorocarbon groups compared with control (p < .01). Final Pao2 (mean +/- SEM) was FC77, 406 +/- 27 mm Hg; perfluorooctylbromide, 332 +/- 32 mm Hg; FC43, 406 +/- 19 mm Hg; control, 68 +/- 8 mm Hg. Paco2 and mean pulmonary arterial pressure were lower in all perfluorocarbon groups compared with control. The ratio of terminal dynamic compliance to total compliance was significantly higher in the FC77 than in the FC43, perfluorooctylbromide, and control groups. Relative gene expression of interleukin-1beta, interleukin-8, P-selectin, E-selectin, and intercellular adhesion molecule-1 in lung tissue was determined by TaqMan real time polymerase chain reaction normalized to hypoxanthineguanine-phosphoribosyl-transferase and was shown to be reduced by all perfluorocarbons.. Aerosol treatment with all the perfluorocarbons investigated improved gas exchange and reduced pulmonary inflammatory reaction independently from molecular structure and vapor pressure of the perfluorocarbons. Although differences in vapor pressure and molecular structure may account for varying optimal dosing strategies, several different perfluorocarbons were shown to be principally suitable for aerosol treatment.

Topics: Administration, Inhalation; Aerosols; Animals; Disease Models, Animal; Drug Evaluation, Preclinical; E-Selectin; Fluorocarbons; Gene Expression; Humans; Hydrocarbons, Brominated; Infant, Newborn; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-1; Interleukin-8; Liquid Ventilation; Lung Compliance; Molecular Structure; P-Selectin; Pulmonary Gas Exchange; Pulmonary Surfactants; Pulmonary Wedge Pressure; Random Allocation; Respiratory Distress Syndrome, Newborn; Swine

Inflammatory reaction and injury in mature lungs are associated with activation of nuclear factor-kappaB (NF-kappaB) to trigger proinflammatory cytokine release. In preterm infants with immature lungs, this mechanism is not yet fully understood, therefore we investigated this mechanism in mechanically ventilated neonates with respiratory distress syndrome (RDS).. Serial samples of the airway aspirates (AA) were obtained during mechanical ventilation from 21 preterm infants with RDS, of which 12 were survivors (birth weight 1.48 +/- 0.32 kg and gestational age 31 +/- 1.5 weeks) and 9 nonsurvivors (1.34 +/- 0.31 kg and 30 +/- 2 weeks). Seven neonates matched for age and birth weight without respiratory disorders served as controls. Alveolar macrophages (AM) of AA were isolated by differential adherence, some were cultured with lipopolysaccharide (LPS) for 1 h. Then, nuclear extracts of AM were analyzed by electrophoretic mobility shift assay for NF-kappaB expression. The NF-kappaB inhibitor (IkappaB-alpha protein) in cytoplasmic extracts was detected by Western blot, and concentrations of IL-1beta and IL-8 in AA by enzyme-linked immunosorbent assay (ELISA).. On day 2 NF-kappaB expression in AM was significantly increased in the survivors and nonsurvivors at 33.3 +/- 9 and 54.8 +/- 10.2 relative density units (RDU) compared to control infants (11.1 +/- 6.7; p < 0.01). Expression of IkappaB-alpha was significantly higher in controls than that in the survivors and nonsurvivors on days 2 and 4. Moreover, in the nonsurvivors of RDS, expression of NF-kappaB was decreased following LPS stimulation in vitro on day 4. IL-1beta and IL-8 levels in the AA supernatant were higher in the survivors than in controls on days 2 and 4, but lower than those of the nonsurvivors on day 2. There were close correlations between the expression of NF-kappaB and levels of IL-1beta (r = 0.78, p < 0.01), and IL-8 (r = 0.81, p < 0.01) in AA.. There were alterations in NF-kappaB activity in the AM of mechanically ventilated preterm neonates with RDS, mediated by decreased synthesis and increased degradation of IkappaB.

Topics: Birth Weight; Enzyme-Linked Immunosorbent Assay; Gestational Age; Humans; I-kappa B Proteins; Infant, Newborn; Infant, Premature, Diseases; Interleukin-1; Interleukin-8; Lipopolysaccharides; Macrophages, Alveolar; NF-kappa B; NF-KappaB Inhibitor alpha; Respiration, Artificial; Respiratory Distress Syndrome, Newborn

In order to predict the late-development of chronic lung disease of prematurity (CLD), cytokines in the cord blood were assessed in this study.. Eighteen premature infants with CLD were enrolled. Cord blood plasma levels of cytokines of these infants and 12 control infants without CLD were measured including interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, soluble TNF receptor-I, and soluble IL-6 receptor using a cytometric bead array and an enzyme-linked immunosorbent assay.. The cord blood IL-6, IL-8, and sTNFR-I levels were significantly elevated in CLD infants compared with those in control (P < .05). IL-1beta, IL-2, IL-4, IL-10, and IFN-gamma were undetectable in both groups. CLD infants with maternal chorioamnionitis had higher IL-6 than those without chorioamnionitis (P < .01). In CLD infants, IL-6 was higher in the infants who required prolonged oxygen therapy (P < .05).. Elevated inflammatory cytokines in the cord blood are associated with the progression to CLD.

Topics: Case-Control Studies; Chronic Disease; Cytokines; Disease Progression; Enzyme-Linked Immunosorbent Assay; Female; Fetal Blood; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Interleukin-6; Interleukin-8; Lung Diseases; Male; Predictive Value of Tests; Receptors, Tumor Necrosis Factor, Type I; Respiratory Distress Syndrome, Newborn

Lung inflammation plays an important role in the pathogenesis of chronic lung disease in preterm infants. To test the hypothesis that prolonged mechanical ventilation induces pulmonary inflammation, we analyzed pro- and anti-inflammatory mediators in bronchoalveolar lavage fluid obtained from ventilated preterm infants having respiratory distress syndrome. Our results show a strong correlation between the duration of mechanical ventilation and the amount of proinflammatory mediators. However, the anti-inflammatory cytokine interleukin 10 remained stable during the whole period of mechanical ventilation. These data support the hypothesis that prolonged mechanical ventilation contributes to the development of chronic lung disease by the induction of lung inflammation without adequate stimulation of the counterregulatory cytokine interleukin 10 in preterm infants with respiratory distress syndrome.

Topics: Bronchoalveolar Lavage Fluid; Chemokine CXCL5; Chemokines, CXC; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Interleukin-10; Interleukin-8; Lung Diseases; Pancreatic Elastase; Pneumonia; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; Time Factors

A high concentration of interleukin (IL)-8 has been observed in the tracheobronchial aspirate of infants with chronic lung disease (CLD), although the pattern varies depending on the type of CLD. Alveolar fluid from patients with adult respiratory distress syndrome (ARDS) also contains an elevated level of IL-8. Recently, the presence of anti-IL-8 autoantibody was demonstrated in the alveolar fluid from patients with ARDS.. The concentration of anti-IL-8 autoantibody in the tracheobronchial aspirate of infants with CLD was measured in order to discover whether there was any correlation with the concentration of IL-8. Similar to IL-8 concentration, the anti-IL-8 IgM antibody concentration in all infants with CLD following intrauterine infection was already high during the first 48 h. However, the concentration in infants with CLD following respiratory distress syndrome began to increase after 11 days of life, in contrast with the rise in IL-8 between 48 h after birth and day 5.. The presence of anti-IL-8 autoantibody may provide a mechanism that limits the bioavailability of free IL-8 in the lungs. In addition, the time lag between the increase in IL-8 and anti-IL-8 IgM autoantibody demonstrated in the present study could be used to estimate the time when the inflammation begins, even if the IL-8 concentration is already high.

Topics: Autoantibodies; Bronchoalveolar Lavage Fluid; Chronic Disease; Humans; Immunoglobulin M; Infant; Infant, Newborn; Interleukin-8; Lung Diseases; Respiratory Distress Syndrome, Newborn

Intraamniotic endotoxin causes chorioamnionitis, which is followed by improved fetal lung function after 4 d in fetal sheep. We evaluated 0.1 mg, 1 mg, 4 mg, and 10 mg endotoxin for inflammation and lung maturation effects after 7 d. Four and 10 mg endotoxin caused similar lung maturation and inflammation in the lung and chorioamnion. The number of neutrophils in cord blood and the inflammatory cells in alveolar lavage and fetal lung tissue increased in a dose-dependent manner. Lower endotoxin doses induced indicators of chorioamnionitis, lung and systemic inflammation without inducing lung maturation. Therefore, some degree of inflammation can occur without subsequent lung maturation. The inflammatory changes caused by 4 mg endotoxin were assessed after 5 h, 24 h, 72 h, and 7 d to discern local versus systemic inflammation after intraamniotic endotoxin. At 5 h active inflammatory cells were in the airways producing hydrogen peroxide, and interleukin-6 and -8 were increased in the cord blood indicating both lung and systemic responses. Cells recruited into the amniotic fluid produced proinflammatory cytokine mRNA for 7 d with no cytokine mRNA in chorioamnion, lung, or spleen after 72 h. The cells in the amniotic fluid may be a source of prolonged fetal exposure to proinflammatory cytokines.

Topics: Amniotic Fluid; Animals; Animals, Newborn; Bronchoalveolar Lavage Fluid; Bronchopulmonary Dysplasia; Chorioamnionitis; Cytokines; Data Interpretation, Statistical; Disease Models, Animal; Endotoxins; Enzyme-Linked Immunosorbent Assay; Female; Fetal Blood; Humans; Infant, Newborn; Inflammation; Interleukin-6; Interleukin-8; Male; Neutrophils; Pregnancy; Pulmonary Surfactants; Random Allocation; Respiratory Distress Syndrome, Newborn; RNA, Messenger; Sheep; Time Factors

In view of cytokine's effects in promoting or inhibiting inflammation, the objective of this study was to explore the characteristics of the proinflammatory cytokine, interleukin-8 (IL-8), and the inhibitory cytokine, interleukin-10 (IL-10), in the bronchoalveolar lavage (BAL) fluid of premature infants suffering from respiratory distress disease. Eighteen premature neonates with respiratory distress disease with gestational age (GA) ranging from 24 to 37 weeks were recruited for study. BAL fluids were collected following endotracheal intubation during an episode of hypoxemia or dyspnea. A series of BAL samples were obtained on day 1, 2, 4 and 7 after intubation for measuring IL-8 and IL-10 levels. The results indicate that premature infants with GA ranging from 24 to 32 weeks had a higher level of IL-8 (p = 0.029), but not level of IL-10 (p = 0.109), in the BAL obtained during the first intubation compared to premature infants with GA ranging from 33 to 37 weeks. The administration of exogenous surfactant did not influence the profiles of IL-8 and IL-10, as compared to those in-patients without treatment. Levels of IL-8 were correlated with IL-10 levels (r = 0.613, p = 0.007) in BAL fluid samples obtained on the day of intubation. The level of IL-8, but not IL-10, was significantly correlated with the duration of intubation. IL-8 and IL-10 levels in BAL fluid samples collected on the day of intubation were correlated with the development of chronic lung disease (CLD). The results suggest that extreme prematurity tends to have increased IL-8 and IL-10 levels in BAL fluid compared to premature infants with older GA, and that these increased levels are associated with the development of CLD.

Topics: Bronchoalveolar Lavage Fluid; Chronic Disease; Humans; Infant; Infant, Newborn; Infant, Premature; Interleukin-10; Interleukin-8; Lung Diseases; Respiratory Distress Syndrome, Newborn

We studied the value of serum interleukin-8 (IL-8) and procalcitonin (PCT) in the early diagnosis of early severe bacterial infection in 58 critically ill ventilated neonates. ELISA was used for determining IL-8 and immunoluminometric assay for PCT. IL-8 and PCT were compared with routinely used serum C-reactive protein (CRP). Neonates were divided into four groups: Ia--proven severe bacterial infection (n = 9), Ib--clinical sepsis (n = 16), II--respiratory distress without bacterial infection (n = 12), and III--various types of neonatal distress (n = 21). Sera were collected on admission, at 24 h and 48 h after admission. There was no significant difference between groups Ia and Ib for either parameter at any time interval. Significant difference was found between group Ia+b (septic neonates) and group II for PCT and CRP at 24 and 48 h, but not for IL-8. There was no difference between group Ia+b and group III except for CRP at 24 h. Diagnostic accuracy was best for PCT on admission and for CRP at 24 h. Serum PCT and IL-8 are not specific markers for early severe bacterial infection in critically ill neonates and are not better than CRP.

Topics: Bacterial Infections; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Humans; Infant, Newborn; Interleukin-8; Protein Precursors; Respiratory Distress Syndrome, Newborn

We have already reported that there are some periods when a high interleukin 8 (IL-8) concentration is observed in the tracheobronchial aspirate of infants with chronic lung disease (CLD), although the changing pattern of the IL-8 concentration varies depending on the type of CLD. Interleukin 8 is known as a neutrophil chemotactic agent. Therefore, we asked whether IL-8 is an important neutrophil chemotactic factor in the tracheobronchial aspirate of infants who later develop CLD.. We measured the neutrophil chemotactic activity of the tracheobronchial aspirate in CLD infants with or without anti-IL-8 antibody. Preincubation with anti-IL-8 immunoglobulinG resulted in a significant reduction of neutrophil chemotactic activity in the tracheobronchial aspirate. In infants with CLD following respiratory distress syndrome, there was a significant relationship between the IL-8 concentration and the neutrophil chemotactic activity of tracheobronchial aspirate without anti-IL-8 antibody, although no significant relationship was seen in infants with CLD following intra-uterine infection or with other CLD.. Interleukin 8 in the tracheobronchial aspirate seems to play a significant role in recruiting neutrophils into the airways of patients with CLD, especially CLD following respiratory distress syndrome. We believe that in this type of CLD, IL-8 in the lung is generated as a result of hyperoxia rather than infection. In this situation, production of other neutrophil chemotactic factors or some factors that inhibit IL-8 activity may be insignificant.

Topics: Chronic Disease; Humans; Infant, Newborn; Infections; Interleukin-8; Lung Diseases; Neutrophil Activation; Respiratory Distress Syndrome, Newborn; Sputum

Migration inhibitory factor (MIF) is known to exert significant pro-inflammatory effects and has the potential to override the anti-inflammatory action of glucocorticoids. In this study we have identified significant quantities of MIF in the alveolar airspaces of patients with acute respiratory distress syndrome (ARDS). We show in alveolar cells from patients with ARDS that MIF augments pro-inflammatory cytokine secretion (TNF alpha and IL-8), anti-MIF significantly attenuates TNF alpha and IL-8 secretion and MIF overrides, in a concentration-related fashion, the anti-inflammatory effects of glucocorticoids. These findings suggest that MIF may act as a mediator sustaining the pulmonary inflammatory response in ARDS and that an anti-MIF strategy may represent a novel therapeutic approach in inflammatory diseases such as ARDS.

Topics: Cells, Cultured; Humans; Immunohistochemistry; Infant, Newborn; Interleukin-8; Lung; Macrophage Migration-Inhibitory Factors; Respiratory Distress Syndrome, Newborn; Tumor Necrosis Factor-alpha

The influx of inflammatory mediators and cells into the tracheobronchial effluent of preterm infants with respiratory distress syndrome (RDS) appears to be important in signaling the development of bronchopulmonary dysplasia (BPD). The mechanism that initiates this early inflammatory response is not well understood. The purpose of this study was to test the hypothesis whether increased interleukin-8 (IL-8), a potent chemoattractant for human neutrophils, appears in the airways of preterm infants with RDS in whom BPD develops before the influx of neutrophils. In addition, airway secretions were analyzed for the cytokine interleukin-6 (IL-6) to test the hypothesis whether this pro-inflammatory cytokine is an early marker of inflammation in preterm infants with RDS who progress to BPD. Sixty-five infants less than 32 weeks gestation with RDS were enrolled on the first day of life and 56 infants completed the study, with 31 recovering from RDS (Non-BPD) and 25 infants progressing to BPD. Infants were excluded from enrollment in the presence of maternal chorioamnionitis, infection at birth, or infection within the first week of life. There were no significant differences in birthweight, gestational age, or prolonged rupture of membranes between the two groups. Serial tracheal aspirates (TA) were collected on days 1, 3, 5, and 7 while the infants remained intubated. Significant elevations of TA neutrophil counts were detected in the BPD group on days 5 and 7. Cell-free TA revealed marked elevations of IL-8 in the BPD group compared to the Non-BPD group [median (25th percentile, 75th percentile), ng/ml epithelial lining fluid (ELF)] on day 1 [BPD 485 (195, 840); Non-BPD 63.1 (28.3, 197), P < 0.05] and day 3 [BPD 740 (319, 1310); Non-BPD 111 (54.3, 337); P < 0.05], while on days 5 and 7, the differences were not statistically significant. Interleukin-6 (IL-6) was measured as a marker of acute inflammation and was not different in the two groups on day 1, but was significantly elevated on day 3 [median (25th percentile, 75th percentile), ng/ml ELF; BPD 297 (62.1, 702); Non-BPD 72 (32.8, 266), P < 0.05] and on day 5 [BPD 270 (136, 672); Non-BPD 86.4 (57.8, 138), P < 0.05]. These studies demonstrate that elevation of IL-8 and IL-6 levels precedes the marked neutrophil influx seen in the TA of preterm infants in whom BPD develop. The presence of IL-8 and IL-6 in TA from these infants suggests that these cytokines either initiate the acute inflammatory cascade in the

Topics: Biomarkers; Bronchopulmonary Dysplasia; Disease Progression; Female; Humans; Infant, Newborn; Infant, Premature; Interleukin-6; Interleukin-8; Male; Neutrophils; Predictive Value of Tests; Prospective Studies; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; Sputum; Trachea

In order to elucidate the role of interleukin 8 (IL-8) on the development of chronic lung disease (CLD) in neonates following an episode of respiratory distress syndrome (RDS), serial and simultaneous measurements of the concentration of IL-8 and granulocyte elastase alpha 1 proteinase inhibitor complex (E-alpha 1 PI) in the tracheobronchial aspirate of very low birthweight infants with RDS were conducted. The concentration of IL-8 and E-alpha 1 PI in infants with CLD was low in the first 48 h of life, but dramatically increased after 48 h. The concentration of IL-8 between 48 h of life and day 5 was significantly correlated to the fraction of inspired oxygen concentration (FiO2) within 48 h of age, but not to the mean airway pressure. Interleukin 8 seemed to stimulate neutrophils to release granulocyte elastase which, in turn, caused lung tissue injury, resulting in the development of CLD. It is suggested that high FiO2 is an important factor causing IL-8 production in the lung.

Topics: Age Factors; Bronchoalveolar Lavage Fluid; Case-Control Studies; Chronic Disease; Humans; Infant, Newborn; Infant, Very Low Birth Weight; Interleukin-8; Neutrophils; Oxygen Inhalation Therapy; Respiratory Distress Syndrome, Newborn; Serpins

Pulmonary neutrophilia characterises both the relatively transient inflammation associated with infant respiratory distress syndrome (IRDS) and the persistent inflammation of chronic lung disease. The possibility that persistently raised markers of inflammation indicate the development of chronic lung disease in low birth weight (< 1730 g) preterm (< 31 weeks) infants was therefore investigated.. Soluble ICAM-1 (sICAM-1) levels in plasma, and interleukin (IL)-8 and myeloperoxidase (MPO) levels in bronchial lavage fluid (BLF) obtained from 17 infants on days 1, 5, and 14 following birth were measured and correlations with the number of neutrophils in BLF sought. Peripheral neutrophils were isolated on Polymorphoprep and chemotactic responsiveness to IL-8 was assessed using micro Boyden chambers.. Sixteen infants developed IRDS and, of these, 10 infants subsequently developed chronic lung disease. Levels of IL-8 in BLF at 14 days of age correlated with the long term requirement for intermittent positive pressure ventilation (IPPV). Interleukin 8 levels in BLF correlated with neutrophil numbers and MPO concentration, suggesting both recruitment and activation in response to this cytokine. Antibody depletion studies showed that approximately 50% of total neutrophil chemotactic activity in BLF was due to IL-8. No difference in peripheral neutrophil chemotactic responsiveness at any age was observed for infants with IRDS or chronic lung disease. Plasma soluble intercellular adhesion molecule (sICAM-1) was higher at 14 days of age in infants who developed chronic lung disease than in those with resolving IRDS, and correlated with severity of disease, as indicated by duration of IPPV.. The results indicate that high levels of plasma sICAM-1 and IL-8 in BLF at day 14 correlate with the development of chronic lung disease and indicate the severity of disease.

Topics: Biomarkers; Bronchoalveolar Lavage Fluid; Chemotaxis, Leukocyte; Chronic Disease; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Intercellular Adhesion Molecule-1; Interleukin-8; Lung Diseases; Neutrophils; Respiratory Distress Syndrome, Newborn

Interleukin-8 (IL-8), soluble intercellular adhesion molecule-1 (sICAM), elastase and neutrophils were assessed in bronchoalveolar lavage fluid from nine infants who developed chronic lung disease (CLD) after respiratory distress syndrome (RDS), seven who had recovered from RDS, and in four control infants. IL-8, sICAM, elastase and neutrophils in bronchoalveolar lavage fluid were increased in the CLD group, the differences being most pronounced at 10 days of age. When babies with and without CLD were compared at 10 days of age, bronchoalveolar lavage fluid from the babies with CLD had significantly increased IL-8 (114.0 vs 12.7 ng/ml), sICAM (19.0 vs 1.1 micrograms/ml), elastase (6.9 vs 0.9 micrograms/ml) and neutrophils (1.9 vs 0.4 x 10(9)/l). In serum the increased concentration of IL-8 observed at birth in the CLD (247 pg/ml) and RDS (192 pg/ml) groups decreased over three weeks to the concentrations observed in the controls (< 70 pg/ml). Persistent inflammation could be a major contributory factor in the development of CLD.

Topics: Bronchoalveolar Lavage Fluid; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Intercellular Adhesion Molecule-1; Interleukin-8; Leukocyte Count; Leukocyte Elastase; Lung Diseases; Neutrophils; Pancreatic Elastase; Respiratory Distress Syndrome, Newborn; Time Factors

Bronchopulmonary dysplasia (BPD) of preterm neonates is associated with an increased recruitment of inflammatory cells into the airways. To evaluate further the role of inflammation in the pathogenesis of BPD, tracheobronchial aspirate fluid of neonates with birth weight < 1200 g (n = 59) was sequentially analyzed in a prospective study.. Tracheobronchial aspirate fluid was assessed for chemotactic activity, neutrophil cell count, concentrations of elastase-alpha 1-proteinase inhibitor and activity of free elastase, concentrations of chemoattractants (complement component C5-derived anaphylatoxin, leukotriene B4, interleukin-8), and albumin concentrations as well as alpha 1-proteinase inhibitor activity. The secretory component for immunoglobulin A was used as reference protein. Only specimens without evidence of microbiological colonization were studied.. In neonates with prolonged respiratory disease (BPD-risk neonates, n = 24, fraction of inspired oxygen > or = 0.3 and/or peak inspiratory pressure > or = 16 cm H2O at day 10 postnatal age, birth weight 892 +/- 36 g, gestational age 27.2 +/- 0.3 weeks) chemotactic activity, cell count, concentrations of the chemoattractants complement component C5-derived anaphylatoxin, leukotriene B4, interleukin-8, as well as levels of elastase-alpha 1-proteinase inhibitor were significantly higher at day 10 and/or day 15 of postnatal age compared with neonates without chronic pulmonary disease (total n = 35; day 10, n = 11; day 15, n = 8). There was no difference in free elastolytic activity. Concentrations of albumin as well as alpha 1-proteinase inhibitor activity were higher in BPD-risk patients on day 15, indicating an increased pulmonary leak.. We conclude that preterm neonates at risk for the development of BPD show an enhanced inflammatory reaction in the lungs and an associated increase in pulmonary microvascular permeability. We speculate that inflammation may play an important role in the pathogenesis of BPD.

Topics: Albumins; alpha 1-Antitrypsin; Bronchopulmonary Dysplasia; Capillary Permeability; Chemotaxis, Leukocyte; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Inflammation; Interleukin-8; Leukocyte Count; Leukotriene B4; Lung; Neutrophils; Pancreatic Elastase; Prospective Studies; Respiratory Distress Syndrome, Newborn; Risk Factors