interleukin-8 and Infant--Premature--Diseases

Neonatal bacterial infections carry a high mortality when diagnosed late. Early diagnosis is difficult because initial clinical signs are nonspecific. Consequently, physicians frequently prescribe antibiotic treatment to newborn infants for fear of missing a life-threatening infection. This study was designed to test the hypotheses that a diagnostic algorithm that includes measurements of interleukin 8 (IL-8) and C-reactive protein (CRP) 1) reduces antibiotic therapy and 2) does not result in more initially missed infections compared with standard management that does not include an IL-8 measurement.. Term and preterm infants who were <72 hours of age and had clinical signs or obstetric risk factors suggesting neonatal bacterial infection but stable enough to wait for results of diagnostic tests were enrolled into the study. A total of 1291 infants were randomly assigned to receive antibiotic therapy according to the guidelines of each center (standard group) or to receive antibiotic therapy when IL-8 was >70 pg/mL and/or CRP was >10 mg/L (IL-8 group). The primary outcome variables were 1) the number of infants treated with antibiotics and 2) the number of infants with infections missed at the initial evaluation.. In the IL-8 group, fewer infants received antibiotic therapy than in the standard group (36.1% [237 of 656] vs 49.6% [315 of 635]). In the IL-8 group, 24 (14.5%) of 165 infants with infection were not detected at the initial evaluation, compared with 28 (17.3%) of 162 in the standard group.. The number of newborn infants who received postnatal antibiotic therapy can be reduced with a diagnostic algorithm that includes measurements of IL-8 and CRP. This diagnostic strategy seemed to be safe.

Topics: Algorithms; Anti-Bacterial Agents; Bacterial Infections; C-Reactive Protein; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Interleukin-8; Sensitivity and Specificity; Unnecessary Procedures

Late-onset sepsis in the NICU is a major problem associated with high morbidity and mortality.. To determine if clinical characteristics, hematological parameters and serial measurements of serum IL-6 and IL-8 can detect late-onset sepsis in premature neonates prior to positive blood cultures.. The study was done in 2 phases. The first phase (S1) was a retrospective evaluation of clinical signs and timing of blood culture positivity in all neonates with late-onset cultures proven sepsis from 1991-1998. The second phase (S2) was a prospective study that enrolled infants > or = 72 hours old, suspected of sepsis based on the presence of criteria identified in S1. At that time (day 0), blood was drawn for a CBC with differential, blood culture, IL-6 and IL-8 levels; cytokine levels were repeated on day 1. Infants with positive cultures were diagnosed as confirmed sepsis; those with negative cultures, as no sepsis.. S1: Of the 48 episodes of culture proven, late-onset sepsis, 54% of the blood cultures were positive by 24 hours and 90% by 48 hours. The most common presenting signs were desaturations (50%) and increased gastric residuals (33%); I/T ratio > 0.16 differentiated between gram-positive, negative and fungal infections (p = 0.007). S2: 27 infants were enrolled. Eight (mean [SEM] gestational age of 28.2 [0.94] weeks; birth weight of 1.15 [0.11] kg) had positive blood cultures; 19 (gestational age of 27.7 [0.9] weeks; birth weight of 1.06 [0.13] kg) had no sepsis. Infants with sepsis were more likely to have apnea/bradycardia (p = 0.002); no differences in hematological profile, as compared to those with no sepsis. Seven (88%) infants had positive blood cultures by 48 hours. Median values of IL-6 (pg/ml) were higher in infants with sepsis vs. those with no sepsis on days 0 [40 vs. 13] (p = 0.03) and 1 [24 vs. 9] (p < 0.001). IL-8 levels were not significantly different.. In both S1 and S2, a majority of the blood cultures were positive by 48 hours. IL-6 levels on days 0 and 1 were significantly higher in infants with confirmed sepsis, prior to the blood culture being positive. IL-6 levels may be useful in the initiation as well as early termination of antibiotic therapy in late-onset neonatal sepsis.

Topics: Biomarkers; Cytokines; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature, Diseases; Interleukin-6; Interleukin-8; Leukocyte Count; Male; Neutrophils; Prospective Studies; Retrospective Studies; Sepsis; Thrombocytopenia; Time

The first objective of this article was to determine the diagnostic accuracy of tumor necrosis factor-alpha, interleukin-6 (IL-6), and interleukin-8 (IL-8) in differentiating infected from noninfected neonates during the first 24 hours of suspected sepsis and to compare them to the currently used laboratory parameters: C-reactive protein (CRP), immature-to-total neutrophil ratio, and leukocyte and platelet count. The secondary objective was to compare the cytokine levels in subpopulations of neonates. Seventy-five premature and 30 term infants were enrolled. Blood samples for the "currently used laboratory tests" and the cytokine levels were obtained at the first suspicion of sepsis ("0-hour") and 18 to 30 hours later ("24-hours"). Patients were classified as septic (48) or nonseptic (57). Thirty-two septic patients had positive blood cultures and 16 showed clinical signs of sepsis. Twenty septic patients had early-onset and 28 had late-onset sepsis. Sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were calculated for each test. Receiver-operating characteristic curves were analyzed to determine the optimal thresholds. A combination of CRP > 10 pg/mL plus IL-6 > 18 pg/mL (sensitivity = 89%, specificity = 73%, PPV = 70%, NPV = 90%) was the best "0-hour" test, and CRP (sensitivity = 78%, specificity = 94%) was the best "24-hours" test. Lower IL-6 at 0-hour (p = 0.018) and IL-8 at 24 hours (p = 0.023) were detected among the patients infected with coagulase-negative staphylococci then with other bacteria. In conclusion, a combination of CRP + IL-6 provided additional diagnostic accuracy for differentiation between septic and nonseptic patients during the first 24 hours of suspected sepsis.

Topics: Biomarkers; C-Reactive Protein; Cytokines; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Inflammation; Interleukin-6; Interleukin-8; Prospective Studies; Reference Values; ROC Curve; Sensitivity and Specificity; Sepsis; Tumor Necrosis Factor-alpha

We tested the hypothesis that inhaled beclomethasone therapy for prevention of bronchopulmonary dysplasia (BPD) reduces pulmonary inflammation. As part of a randomized, placebo-controlled trial, interleukin-8 (IL-8) and interleukin-1 receptor antagonist (IL-1ra) concentrations in tracheal aspirates were measured as markers of pulmonary inflammation. On study days 1 (baseline), 8, 15, and day 28 of age, samples were obtained from enrolled infants (birth weights <1,251 g, gestational age <33 week, 3 to 14 days of age) who remained ventilated and had not received systemic glucocorticoid therapy. Cytokine levels (pg/microg of free secretory component of immunoglobulin A) were compared between groups. We determined whether baseline cytokine levels modified treatment effect regarding subsequent need for systemic glucocorticoid therapy or occurrence of BPD (age 28 days). Tracheal aspirates were obtained from 161 infants (77 receiving beclomethasone, 84 receiving placebo). Median IL-8 levels were lower in beclomethasone versus placebo infants on study days 8 (82.9 vs. 209.2, P < 0.01) and 15 (37.4 vs. 77.4, P < 0.03) after controlling for antenatal glucocorticoid therapy and maternal race. Median IL-1ra levels were lower in beclomethasone versus placebo infants only on study day 8 (86.5 vs. 153.3, P < 0.01). Fewer beclomethasone infants with baseline IL-8 levels in the interquartile range required systemic glucocorticoid therapy (beclomethasone 30.6% vs. placebo 65.8%, P < 0.01) or developed BPD (beclomethasone 42.4% vs. placebo 69.4%, P < 0.03). We conclude that early-inhaled beclomethasone therapy was associated with a reduction in pulmonary inflammation after 1 week of therapy. Beclomethasone-treated infants with moderately elevated baseline IL-8 levels received less subsequent systemic glucocorticoid therapy and had a lower incidence of BPD than nontreated infants.

Topics: Administration, Inhalation; Beclomethasone; Body Fluids; Bronchopulmonary Dysplasia; Female; Glucocorticoids; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Inflammation Mediators; Interleukin-8; Male; Receptors, Interleukin-1; Respiration, Artificial; Trachea

The purpose of this study was to compare the effects of daily inhaled beclomethasone (3 x 500 microg) started on day 3 of life, with that of systemic dexamethasone (0.5 mg/kg/day) started between days 11-13 on clinical variables, lung inflammation, and pulmonary microvascular permeability in preterm infants at risk for chronic lung disease (CLD). Following administration of surfactant, preterm neonates with RDS and a birth weight of less than 1,200 g were included in this comparative observational pilot study when still mechanically ventilated and with an oxygen requirement on the third day of life. The patients (gestational age 26.1+/-0.9 weeks, birth weight 826+/-140 g, mean+/-SD) were alternately allocated to prophylactic treatment with inhaled beclomethasone (n = 7), or to early systemic dexamethasone therapy after day 10 of life, if clinically indicated (n = 9). Pulmonary inflammation and lung permeability were assessed by analyzing the levels of interleukin-8, elastase alpha1 proteinase inhibitor, free elastase activity, and albumin in tracheal aspirates on days 10 and 14 of life. The secretory component of IgA served as reference protein. We observed no significant differences in the concentrations of interleukin-8, elastase alpha1 proteinase inhibitor, and albumin between the two groups on day 10 of life. On day 14, 3 (median; range, 1-3) days following initiation of dexamethasone treatment, concentrations of the inflammatory mediators and of albumin were significantly lower in the group on systemic steroid therapy than in the group treated with inhaled steroids (P < 0.01). Additionally, there was a significant difference in oxygen requirements between both groups on day 14. In the group treated with inhaled steroids, concentrations of the inflammatory mediators, albumin, and oxygen requirements did not show a difference between day 10 and 14. We conclude that, in contrast to systemic dexamethasone treatment, a 12-day course of inhaled beclomethasone does not affect lung inflammation and pulmonary microvascular permeability in preterm infants at risk for CLD within the first 2 weeks of life.

Topics: Administration, Inhalation; Beclomethasone; Capillary Permeability; Chronic Disease; Dexamethasone; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Inflammation Mediators; Interleukin-8; Lung; Lung Diseases; Pancreatic Elastase; Pilot Projects; Protease Inhibitors; Respiration, Artificial

In cases of premature rupture of membranes (PROM), an early detection of fetal infection is necessary in order to weigh infectious complications against prematurity. As routine parameters (leukocytes, C-reactive protein (CRP), fever, and fetal tachycardia) lack satisfactory sensitivity and specificity, this study evaluates whether the determination of interleukin-6 (IL-6), interleukin-8 (IL-8) or soluble interleukin-2 receptor (IL-2R) in maternal serum could supplement or replace routine inflammation parameters.. In this prospective study results of clinical and laboratory parameters were investigated with respect to neonatal infection in 71 patients with PROM. IL-6, IL-8 and IL-2R were determined by enzyme immunoassays.. Best specificity and sensitivity could be demonstrated for CRP and IL-6. Both elevation of CRP and IL-6 correlated significantly (p<0.01 and p<0.001, respectively) with the onset of neonatal infection. At a cutoff of 11 pg/ml, IL-6 reaches a sensitivity of 81% and a specificity of 76%; CRP a specificity of 76% (cutoff 1.2 mg/dl) and a sensitivity of 56%. In 4/16 (25%) cases developing neonatal infection, IL-6 increased earlier than CRP. IL-8 and IL-2R results showed a less significant correlation with fetal outcome.. Determination of IL-6 in maternal serum can significantly contribute to an earlier detection of fetal infection in patients with PROM.

Topics: Area Under Curve; Bacterial Infections; C-Reactive Protein; Female; Fetal Membranes, Premature Rupture; Gestational Age; Humans; Infant, Newborn; Infant, Premature, Diseases; Interleukin-6; Interleukin-8; Leukocytosis; Predictive Value of Tests; Pregnancy; Pregnancy Outcome; Prospective Studies; Receptors, Interleukin-2; ROC Curve; Sensitivity and Specificity; Time Factors

To determine if erythromycin given from birth reduces the inflammatory response and the incidence and severity of chronic lung disease.. Seventy five infants less than 30 weeks of gestation and ventilated from birth for lung disease were randomly assigned to receive erythromycin intravenously for 7 days or to no treatment. Ureaplasma urealyticum was detected in tracheal secretions by culture and polymerase chain reaction. Differential cell counts were obtained from bronchoalveolar lavage fluid collected daily for 5 days and concentrations of the cytokines interleukins IL-1 beta and IL-8, and tumour necrosis factor alpha (TNF-alpha) were measured. Chronic lung disease (CLD) was defined as oxygen dependency at 36 weeks of gestation.. Nine infants (13%) were positive for U urealyticum. The inflammatory cytokines in the lungs increased over the first 5 days of life in all babies, but no association was found between their concentrations and the development of CLD. Those treated with erythromycin showed no significant differences from the non-treated group in the differential cell counts or concentrations of the cytokines. The two groups had a similar incidence of CLD. Babies infected with U urealyticum did not have a more pronounced cytokine response than those without infection. Chorioamnionitis was associated with significantly higher concentrations of IL-1 beta and IL-8 on admission: these babies had less severe acute lung disease and developed significantly less CLD.. U urealyticum in the trachea was not associated with an increased inflammatory response in preterm infants. Erythromycin did not reduce the incidence or severity of CLD.

Topics: Anti-Bacterial Agents; Chronic Disease; Erythromycin; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Interleukin-1; Interleukin-8; Lung Diseases; Male; Trachea; Ureaplasma Infections; Ureaplasma urealyticum

Neonatal sepsis accounts for 0.97% of all disability-adjusted life years worldwide. Interleukin-6 has been used in sepsis diagnosis, but cut-off values are missing.. Neonates admitted to the neonatal wards with measurements of serum interleukin-6 born between September 2015 and September 2019 were retrospectively analysed. Mean serum interleukin-6 values of patients who never had increased laboratory parameters of infection nor died during their stay and mean interleukin-6 values on the day of blood sampling for a later positive culture in patients with culture-confirmed sepsis were analysed for each time period.. In all, 8.488 values in 1.695 neonates, including 752 very-preterm-infants and 701 very-low-birthweight infants, were analysed. The AUC for interleukin-6 was 0.84-0.91 in all neonates, 0.88-0.89 in very-preterm and 0.89-0.91 in very-low-birthweight infants. Using interleukin-6 cut-off values of 80 pg/ml on day of life 1, 40 pg/ml on day of life 2-7 and 30 pg/ml after day of life 7, a sensitivity of 75% and a specificity of 81% for culture-confirmed sepsis were achieved. In very-preterm infants, the corresponding values were 74% for sensitivity and 83% for specificity and in very-low-birthweight infants 74% and 86%, respectively.. Serum interleukin-6 has high accuracy for the detection of neonatal sepsis.. Serum interleukin-6 can be used with high accuracy to detect sepsis in neonates with the cut-off values of 80 pg/ml on day of life 1, 40 pg/ml on day of life 2-7 and 30 pg/ml after day of life 7. Serum interleukin-6 can be used with high accuracy to detect sepsis in neonates and very-preterm as well as very-low-birthweight infants. Interleukin-6 values display distinct cut-off values depending on the chronological age of the infant. Our article provides the first cut-off values for interleukin-6 in the first days of life in neonates.

Topics: Biomarkers; C-Reactive Protein; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Interleukin-6; Interleukin-8; Neonatal Sepsis; Retrospective Studies; Sensitivity and Specificity; Sepsis

Necrotizing enterocolitis (NEC) often leads to gastrointestinal emergency resulting high mortality in very low birth weight infants (VLBWIs) requiring surgery. To date, few studies have explored the role of serum cytokines in the development of feeding intolerance (FI) or NEC outcomes in VLBWIs. Infants born weighing <1500 g or of 32 weeks of gestational age were prospectively enrolled from May 2018 to Dec 2019. We measured several cytokines routinely within 72 h of life, even before NEC-like symptoms developed. NEC or FI group comprised 17 (27.4%) infants, and 6 (9.7%) infants had surgical NEC. The gestational age and birth weight were significantly lower in the NEC or FI group with more prematurity-related complications. The surgical NEC group also demonstrated significantly lower gestational age and birth weight along with more infants experiencing refractory hypotension within a 1 week of life, pulmonary hypertension, and patent ductus arteriosus. IL-10 levels were significantly higher in the NEC or FI group, whereas IL-8 levels were significantly higher in the infants with surgical NEC. Our findings indicated to IL-8 can predict surgical NEC while increased IL-10 can predict NEC development in VLBWIs.

Topics: Biomarkers; Cytokines; Enterocolitis, Necrotizing; Gestational Age; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Inflammation Mediators; Interleukin-10; Interleukin-8; Prognosis; Prospective Studies

Early identification of infants at risk for complications from patent ductus arteriosus (PDA) may improve treatment outcomes. The aim of this study was to identify biochemical markers associated with persistence of PDA, and with failure of pharmacological treatment for PDA, in extremely preterm infants.. Infants born at 22-27 weeks' gestation were included in this prospective study. Blood samples were collected on the second day of life. Fourteen biochemical markers associated with factors that may affect PDA closure were analyzed and related to persistent PDA and to the response of pharmacological treatment with ibuprofen.. High levels of B-type natriuretic peptide, interleukin-6, -8, -10, and -12, growth differentiation factor 15 and monocyte chemotactic protein 1 were associated with persistent PDA, as were low levels of platelet-derived growth factor. High levels of erythropoietin were associated with both persistent PDA and failure to close PDA within 24 h of the last dose of ibuprofen.. High levels of inflammatory markers were associated with the persistence of PDA. High levels of erythropoietin were associated with both the persistence of PDA and failure to respond to pharmacological treatment.

Topics: Biomarkers; Chemokine CCL2; Ductus Arteriosus, Patent; Echocardiography; Growth Differentiation Factor 15; Humans; Ibuprofen; Infant, Extremely Premature; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Inflammation; Interleukin-10; Interleukin-12 Subunit p35; Interleukin-6; Interleukin-8; Natriuretic Peptide, Brain; Platelet-Derived Growth Factor; Prospective Studies; Risk; Sweden

Morbidities of impaired immunity and dysregulated inflammation are common in preterm infants. Postnatal Intestinal development plays a critical role in the maturation of the immune system and is, in part, driven by exposure to an enteral diet.. The aim of this study was to evaluate the influence of the timing of the first enteral feeding on intestinal inflammation and risk of disease.. 130 infants <33 weeks' gestation were studied. Maternal and infant data were abstracted from the medical record. Single and multiplex ELISA assays quantified cytokines from fecal and serum samples at two weeks postnatal age.. A delay in enteral feedings after the third postnatal day is associated with a 4.5 (95% CI 1.8-11.5, p=0.002) fold increase in chronic lung disease, 2.9 (1.1-7.8, p=0.03) fold increase in retinopathy of prematurity, and 3.4 (1.2-9.8, p=0.02) fold increase in multiple comorbidities compared to infants fed on or before the third day. Additionally, a delay in the initiation of feedings is associated with increased fecal IL-8 levels and a decreased IL-10:IL-8 ratio.. A delay in enteral feeding is associated with intestinal inflammation and increased risks of morbidities. To improve neonatal outcomes, early nutritional practices need to be reevaluated.

Topics: Adult; Enteral Nutrition; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Inflammation; Interleukin-10; Interleukin-8; Intestinal Mucosa; Intestines; Postnatal Care; Time Factors

The purpose of this study was to evaluate the predictiveness of circulating interleukin (IL)-8 for 60-day mortality in premature infants with necrotizing enterocolitis (NEC).. NEC affects up to 5% of premature infants and remains a leading cause of mortality among neonates.. A total of 113 infants with surgically (n=50) or medically (n=63) treated NEC were retrospectively analyzed. Laboratory parameters including serum IL-8 were assessed at the diagnosis of NEC and during the preoperative workup.. The 60-day mortality was 19% (22/113), 10% (6/63) in medical and 33% (16/50) in surgical NEC. IL-8 levels significantly correlated with 60-day mortality (odds ratio: 1.38; CI 1.14-1.67; p=0.001). Median IL-8 levels at diagnosis were significantly higher in neonates who were later treated surgically (median=2625 pg/ml; range: 27-7500) compared with those treated medically (median=156 pg/ml; range: 5-7500; p<0.001). The AUC to discriminate between medical and surgical NEC was 0.82 (CI, 0.74-0.90), and an exploratory IL-8 cutoff point could be established at 1783 pg/ml (sensitivity of 90.5%; specificity of 59.2%).. Our findings that serum IL-8 (i) correlates directly with 60-day mortality and (ii) differs significantly between medically and surgically treated infants may change the process of therapeutic decision making in NEC.

Topics: Biomarkers; Diseases in Twins; Enterocolitis, Necrotizing; Female; Gestational Age; Hospital Mortality; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Interleukin-8; Kaplan-Meier Estimate; Male; Odds Ratio; Platelet Count; Predictive Value of Tests; Prognosis; Vasoconstrictor Agents

Intra-uterine growth restriction (IUGR) may induce significant metabolic and inflammatory anomalies, increasing the risk of obesity and CVD later in life. Similarly, alterations in the adipose tissue may lead to metabolic changes in children with a history of extra-uterine growth restriction (EUGR). These mechanisms may induce alterations in immune response during early life. The aim of the present study was to compare pro-inflammatory markers in prepubertal EUGR children with those in a reference population. A total of thirty-eight prepubertal children with a history of EUGR and a reference group including 123 healthy age- and sex-matched children were selected. Perinatal data were examined. In the prepubertal stage, the concentrations of inflammatory biomarkers were measured in both groups. The serum concentrations of C-reactive protein (CRP) and plasma concentrations of hepatocyte growth factor (HGF), IL-6, IL-8, monocyte chemotactic protein type 1 (MCP-1), neural growth factor, TNF-α and plasminogen activator inhibitor type 1 were determined. The plasma concentrations of inflammatory biomarkers CRP, HGF, IL-8, MCP-1 and TNF-α were higher in the EUGR group than in the reference group (P< 0·001). After adjustment for gestational age, birth weight and length, blood pressure values and TNF-α concentrations remained higher in the EUGR group than in the reference group. Therefore, further investigations should be conducted in EUGR children to evaluate the potential negative impact of metabolic, nutritional and pro-inflammatory changes induced by the EUGR condition.

Topics: Adult; Biomarkers; Birth Weight; Blood Pressure; C-Reactive Protein; Case-Control Studies; Chemokine CCL2; Child; Female; Gestational Age; Growth Disorders; Hepatocyte Growth Factor; Humans; Infant, Premature; Infant, Premature, Diseases; Inflammation; Interleukin-6; Interleukin-8; Male; Tumor Necrosis Factor-alpha

To see if the systemic inflammation profile of 123 infants born before the 28th week of gestation who had intraventricular hemorrhage without white matter injury differed from that of 68 peers who had both lesions, we compared both groups to 677 peers who had neither. Cranial ultrasound scans were read independently by multiple readers until concordance. The concentrations of 25 proteins were measured with multiplex arrays using an electrochemiluminescence system. Infants who had both hemorrhage and white matter injury were more likely than others to have elevated concentrations of C-reactive protein and interleukin 8 on days 1, 7, and 14, and elevated concentrations of serum amyloid A and tumor necrosis factor-α on 2 of these days. Intraventricular hemorrhage should probably be viewed as 2 entities: hemorrhage alone and hemorrhage with white matter injury. Each entity is associated with inflammation, but the combination has a stronger inflammatory signal than hemorrhage alone.

Topics: Age Factors; C-Reactive Protein; Cerebral Hemorrhage; Female; Gestational Age; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Inflammation; Interleukin-8; Leukoencephalopathies; Male; Odds Ratio; Serum Amyloid A Protein; Tumor Necrosis Factor-alpha; Ultrasonography, Doppler

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 2 weeks of ventilation are more likely than shorter durations of ventilation to be accompanied by high blood concentrations of pro-inflammatory proteins indicative of systemic inflammation, and by low concentrations of proteins that might protect from inflammation-mediated organ injury.

Topics: Chemokine CCL2; Chemokine CCL4; Chemokine CCL5; Chemokines; Chorioamnionitis; Cytokines; Female; Humans; Infant, Extremely Premature; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-1beta; Interleukin-8; Male; Matrix Metalloproteinase 9; Pregnancy; Respiration, Artificial; Systemic Inflammatory Response Syndrome; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

Acute hyperglycemia is considered as a pro-inflammatory state and is related to an adverse outcome in critically ill adults. Neonates are susceptible to infections and systemic inflammatory response syndrome induced by pro-inflammatory cytokines. This study focuses on the interaction between neonatal glucose homeostasis and the pro-inflammatory cytokine production in term and preterm infants in-vitro.. We analyzed the pro-inflammatory cytokine production in whole cord blood of term infants (n = 10), preterm infants > 32 weeks (n=16) and preterm infants ≤32 weeks of gestational age (n = 13) and in adult controls (n=14) using an in-vitro sepsis-model. Whole blood was pre-incubated with different concentrations of glucose (0-1000 mg/dl) and insulin (0-62.5 IE/l) and stimulated with lipopolysaccharide. The intracytoplasmatic TNF-α, IL-6, and IL-8 response was measured by flow cytometry.. In-vitro hyperglycemia induced a dose-dependent increase of IL-8 in all age groups while TNF-α was demonstrated to be stimulated by glucose in cord blood samples of preterm infants ≤32 weeks of gestational age and term infants. In contrast, insulin showed no significant effects on pro-inflammatory cytokine production in-vitro.. Acute hyperglycemia may induce pro-inflammatory cytokine responses in neonatal whole blood in-vitro. These data provide a basis for further in-vitro signal transduction studies and in-vivo investigations about the significance of neonatal glucose homeostasis and its impact on long-term outcome of this susceptible patient cohort.

Topics: Cytokines; Fetal Blood; Gestational Age; Glucose; Humans; Hyperglycemia; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Insulin; Interleukin-6; Interleukin-8; Lipopolysaccharides; Models, Biological; Sepsis; Tumor Necrosis Factor-alpha

To examine the association among interleukin-6, interleukin-8, tumor necrosis factor-α, interleukin-10, and interleukin-1β and white matter injury in very-low-birth-weight infants with clinical sepsis and to help predict infants at risk for development of white matter injury.. A prospective cohort study was carried out.. Neonatal intensive care unit.. Very low birth weight infants with clinical early-onset sepsis. Exclusion criteria were death before 14 days, major malformations, and congenital infections.. Ultrasound brain scans were carried out on the third day and weekly until the sixth week of life or discharge and confirmed by a magnetic resonance image performed in the first year. Plasma was assayed for interleukin-6, interleukin-8, tumor necrosis factor-α, interleukin-10, and interleukin-1β in the same sample collected for sepsis work-up. Mann-Whitney, chi-square, t tests, multiple regression, and receiver operating characteristic analysis were applied.. From July 2005 to October 2007 we studied 84 very-low-birth-weight infants, 27 (32%) with white matter injury, and 57 (68%) control subjects (with no white matter injury). Proven early-onset sepsis and necrotizing enterocolitis were high risk for white matter injury after adjustment for gestational age and birth weight (relative risk, 3.04; 1.93-4.80 and relative risk, 2.2; 1.31-3.74, respectively). Interleukin-6, interleukin-8, and tumor necrosis factor-α levels were higher in infants with white matter injury than in control subjects (p < .0001). Interleukin-1β and interleukin-10 were similar. The areas under the curve for interleukin-6, interleukin-8, and tumor necrosis factor-α were 0.96 (0.92-0.99), 0.97 (0.94-1.0), and 0.93 (0.86-0.99), respectively. Interleukin-8 ≥100 pg/mL was the best predictor of white matter injury; the sensitivity and specificity were 96% and 83%, respectively, and negative predictive value was 98%.. Very-low-birth-weight infants with proven early-onset sepsis, necrotizing enterocolitis, and high plasma levels of interleukin-6, interleukin-8, and tumor necrosis factor-α are at high risk for white matter injury.

Topics: Brain Injuries; Cytokines; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Interleukin-10; Interleukin-1beta; Interleukin-6; Interleukin-8; Leukoencephalopathies; Male; Prospective Studies; Risk Factors; Sepsis; Tumor Necrosis Factor-alpha; Ultrasonography

Various cytokines have been associated to the occurrence of bronchopulmonary dysplasia (BPD) in preterm neonates.. To establish an association between cord blood cytokines and BPD, so that they could be used, in clinical practice, as early markers of BPD.. Preterms less than 30 weeks gestational age, were analysed by ELISA microassay for venous cord blood IL-1β, IL-6, IL-8, TNF-α and IL-10, and compared between the BPD and non-BPD groups.. One hundred and fifty neonates completed the study; 31 (21%) small for gestational age (SGA); 16 were deceased before 28 days of life; 36 developed mild BPD and 20 developed moderate/severe BPD. Elevated cord blood IL-8 was associated with death or moderate/severe BPD. SGA patients with moderate/severe BPD presented higher cord blood values of IL-8, lower IL-6 and IL-10 when compared with SGA without moderate/severe BPD; and higher IL-8 levels when compared with patients without moderate/severe BPD.. These results support an association between cord blood IL-8 and moderate/severe BPD, independently of the intra-uterine growth; and the association of cord blood IL-6 and IL-10 and moderate/severe BPD in SGA preterm newborns.

Topics: Biomarkers; Bronchopulmonary Dysplasia; Early Diagnosis; Female; Fetal Blood; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Small for Gestational Age; Interleukin-10; Interleukin-6; Interleukin-8; Male; Tumor Necrosis Factor-alpha

To test whether chronic bronchial inflammation may be a contributing risk factor for persistent airflow limitation in children born before 32 weeks of gestation in later life.. Thirty-six of 160 children born before 32 completed weeks of gestation who were born between 1988 and 1992 were recruited at a median age of 11 years. Eighteen age-matched children born at term were controls; 47% of the premature infants and 61% of the term born children produced sputum of sufficient quality for interleukin (IL)-8, cell numbers, and differential counts.. Compared with term born children, sputum from the premature group had a higher proportion of neutrophils (62% vs 3.8%; P < .001) and higher IL-8/protein values (1.93 μg/g vs 0.64 μg/g; P = .008). Forced expiratory flow 25%-75% and forced expiratory volume in 1 second/vital capacity were significantly lower (73.4 % vs 116% predicted, P = .002 and 97% vs 101%, P = .012, respectively). Lung function values and sputum indices did not correlate. IL-8/protein and neutrophil percentages correlated significantly with decreasing gestational age (Spearman rank coefficient = -0.58, P = .020 and -.70, P =.03 respectively).. A significant proportion of school children born very preterm demonstrate persistent peripheral airway obstruction that is accompanied by neutrophilic lower airway inflammation.

Topics: Airway Obstruction; Biomarkers; Bronchitis, Chronic; Case-Control Studies; Child; Cross-Sectional Studies; Female; Forced Expiratory Flow Rates; Forced Expiratory Volume; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Interleukin-8; Logistic Models; Male; Neutrophils; Sputum; Surveys and Questionnaires; Vital Capacity

The aim of this study was to test the predictive value of interleukin (IL) 8 in the assessment of intestinal involvement in necrotizing enterocolitis (NEC).. Forty infants with surgically treated NEC were classified into 3 groups based on intestinal involvement during laparotomy: focal (n = 11), multifocal (n = 16), and panintestinal (n = 13). Preoperatively obtained serum levels of IL-8, C-reactive protein, white blood cell count, and platelet count were correlated with intestinal involvement using logistic regression models.. Interleukin 8 correlated significantly with intestinal involvement in infants with surgically treated NEC (odds ratio, 1.74; confidence interval, 1.27-2.39; P < .001). An exploratory IL-8 cutoff value of 449 pg/mL provided a specificity of 81.8% and sensitivity of 82.8% to discriminate focal from multifocal and panintestinal disease. An IL-8 cutoff value of 1388 pg/mL provided a specificity of 77.8% and a sensitivity of 76.9% to discriminate panintestinal disease from focal and multifocal disease.. To our knowledge, this is the first study to demonstrate a significant correlation of IL-8 with intestinal involvement in advanced NEC in a large patient population. Our results indicate that IL-8 may be a promising biomarker for assessing intestinal involvement in infants with advanced NEC.

Topics: Bacteremia; Biomarkers; C-Reactive Protein; Enterocolitis, Necrotizing; Female; Gestational Age; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Interleukin-8; Intestines; Laparotomy; Leukocyte Count; Male; Pneumatosis Cystoides Intestinalis; Predictive Value of Tests; Preoperative Care; ROC Curve; Sensitivity and Specificity; Severity of Illness Index

Topics: Airway Obstruction; Bronchitis, Chronic; Female; Humans; Infant, Premature, Diseases; Interleukin-8; Male; Neutrophils; Sputum

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

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

Persistence of neutrophils in the tracheal fluid of premature infants is associated with chronic lung disease (CLD). Interleukin-8 (IL-8) is a potent neutrophil chemoattractant. This study investigated whether IL-8 is increased in the bronchoalveolar lavage fluid of premature infants with different types of CLD.. Forty two very low birth weight infants who required mechanical ventilation were recruited. Twenty eight of these infants developed CLD and 14 infants recovered without developing CLD. Four additional infants receiving mechanical ventilation for non-respiratory reasons were also enrolled as controls. CLD was defined as requirement for supplemental oxygen at 28 days of age and chest radiograph showing characteristic appearance. CLD was further classified into 3 subtypes: bronchopulmonary dysplasia (BPD), Wilson-Mikity syndrome (WMS) and chronic pulmonary insufficiency of prematurity (CPIP).. IL-8 in bronchoalveolar lavage fluid was significantly increased in the CLD group by 8 days of age compared to those who did not develop CLD (p < 0.05). For infants without CLD, IL-8 increased from 963 pg/mL on day 1 after delivery to 1463 pg/mL on day 4, and decreased to 1,000 pg/mL on day 8. For infants with BPD, IL-8 increased from 925 pg/mL on day 1 after delivery to 2,650 pg/mL on day 8, and then gradually decreased to 1,500 pg/mL on day 28. Infants with WMS had significantly higher IL-8 from the first day after delivery (4,567 pg/mL) than infants with BPD or CPIP and this difference persisted to age 28 days (2475 pg/mL).. Persistent inflammation could be a major contributory factor in the development of CLD. The different patterns of response to inflammation in different types of CLD may have implications for the design of appropriate strategies to prevent and treat CLD.

Topics: Bronchoalveolar Lavage Fluid; Chronic Disease; Humans; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Interleukin-8; Lung Diseases; Respiration, Artificial

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

The peptide endothelin-1 (ET-1) plays an unknown role in the pathogenesis and progression of two important neonatal pulmonary disorders, chronic lung disease (CLD) of prematurity and persistent pulmonary hypertension of the newborn (PPHN). Inhaled nitric oxide (INO) is a proven vasodilator therapy in PPHN and is an experimental therapy in CLD. We sought to determine the effects, if any, of the interaction of inhaled INO with ET-1 in these two separate disorders. Infants (n=21) with PPHN (mean gestation age, 39.4 weeks; mean birth weight, 3470 g) were treated with INO. All infants were <72 h of age at baseline. Plasma obtained at baseline and after 24 h of INO therapy was assessed for ET-1. The change in ET-1 levels with INO was inversely correlated with change in arterial partial pressure of O(2) (r=-0.71, P=0.0003). A separate group of 33 patients with CLD (mean gestational age, 27 weeks; mean birth weight, 740 g; mean age, 19 days) had tracheal aspirate levels of ET-1 obtained before, during, and after 7 days' administration of INO. Values were normalized by soluble secretory component of IgA. Tracheal aspirate ET-1 levels were detectable before INO therapy. There was no significant change during or after treatment with INO. There was not a significant correlation between baseline fractional inspired O(2) and ET-1 levels. There was a non-significant trend in the correlation between the change in ET-1 and the change in interleukin-8 levels in tracheal aspirate. This report confirms the presence of ET-1 in tracheal aspirate of premature infants who are developing CLD and reaffirms the presence of ET-1 in plasma of infants with PPHN. Short-term INO therapy was associated with a decrease in plasma ET-1 levels in PPHN, but did not affect tracheal aspirate ET-1 in CLD. Given the vasconstrictive, profibrotic, and proinflammatory properties of ET-1, specific ET-1 receptor antagonists could be considered as candidates for trials as adjunct therapy in either or both of these disorders.

Topics: Administration, Inhalation; Biomarkers; Endothelin-1; Humans; Hypertension, Pulmonary; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Interleukin-8; Nitric Oxide; Persistent Fetal Circulation Syndrome; Pulmonary Disease, Chronic Obstructive

To elucidate the mechanism of the development of chronic lung disease (CLD) in infants without respiratory distress syndrome or intra-uterine infection, we serially measured the concentrations of interleukin 8 (IL-8) and granulocyte elastase alpha 1 proteinase inhibitor complex (E-alpha 1 PI) and elastase activity in the tracheobronchial aspirate of very low birth weight infants without respiratory distress syndrome or intra-uterine infection until day 28. IL-8 concentration and elastase activity between day 21 and 28 in infants who developed CLD later were significantly higher compared with those in infants who did not develop CLD. E-alpha 1 PI concentration between day 25 and 28 in infants who developed CLD later was significantly higher compared with those in infants who did not develop CLD. The area under the curve of the IL-8 and E-alpha 1 PI concentrations and elastase activity between day 1 and day 28 in infants with CLD was significantly higher than those in infants without CLD. These data suggest that the lung tissue injury caused by the enzymes from neutrophils accumulated and activated by IL-8 also play an important role in the development of this type of CLD.

Topics: Bronchoalveolar Lavage Fluid; Chronic Disease; Female; Humans; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Interleukin-8; Leukocyte Elastase; Lung Diseases; Male

The inflammatory indicators in the tracheobronchial aspirate (TA) of 81 ventilated preterm infants with microbial colonisation of the airways and in non-colonised neonates were analysed on the first day of life. TA was assessed for chemotactic activity, neutrophil cell count, and concentrations of leukotriene B4, C5a, interleukin-1, interleukin-8, elastase-alpha 1-proteinase inhibitor, free elastase and albumin. Concentrations of mediators were related to concentrations of the secretory component of IgA. The infants' gestational age was mean (SD) 27.9 (2.0) weeks, birthweight 945 (179) g. In 12 infants (15%) microbial colonisation of the airways was present (Ureaplasma urealyticum n = 7; bacteria n = 5). Compared with non-colonised neonates (n = 69), chemotactic activity, neutrophil count, and concentrations of interleukin-1, leukotriene B4 and elastase-alpha 1-proteinase inhibitor were significantly higher in the colonised group. The difference was most pronounced for IL-1 concentrations, both with and without correction for secretory component. There was also a trend towards increased concentrations of interleukin-8 in the latter group. There were no differences for concentrations of C5a and albumin in the TA of both groups. It is concluded that airway colonisation with U urealyticum or bacteria at birth is associated with a clinically relevant bronchopulmonary inflammatory response. Increased concentrations of interleukin-1 in TA on the first day of life may be a marker of perinatal colonisation of the airways.

Topics: alpha 1-Antitrypsin; Bacterial Infections; Biomarkers; Bronchi; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Interleukin-1; Interleukin-8; Leukocyte Elastase; Leukotriene B4; Male; Pancreatic Elastase; Prospective Studies; Trachea; Ureaplasma Infections; Ureaplasma urealyticum

Chronic lung disease (CLD) of prematurity is associated with an initial increase in pulmonary neutrophils followed by pulmonary fibrosis. We determined whether the proinflammatory cytokines, IL-1 beta and IL-6, were increased in the bronchoalveolar lavage fluid obtained from nine infants (median gestation 25 wk, birthweight 820 g) who developed CLD, seven (28 wk, 1110 g) who recovered from the respiratory distress syndrome (RDS), and four (38 wk, 2690 g) control infants. IL-1 beta and IL-6 protein were both increased in the bronchoalveolar lavage fluid from the CLD groups when compared with the RDS and control groups. This difference for both the cytokines was most marked on d 10 of age, when results from infants with and without CLD were compared (IL-1 beta, 4.6 versus 1.1 ng/mL, p < 0.05; and IL-6, 9.5 versus 1.5 ng/mL, p < 0.05). Immunocytochemistry of lavage cells for IL-1 beta, IL-6, and IL-8 protein showed alveolar macrophages to contain all three cytokines, with lesser staining evident in neutrophils, and in epithelial cells occasionally obtained by lavage. The contribution of alveolar macrophages and luminal cells to the increase in IL-6 and IL-1 was determined by performing semiquantitative reverse transcription-polymerase chain reactions on RNA extracted from lavage cells. IL-6 mRNA expression was increased in lavage cells from the CLD infants when compared with the RDS group. However, the expression for IL-1 beta and IL-8 mRNA was similar in both groups. These results suggest that IL-1 beta, IL-6, and IL-8 may contribute to the pathogenesis of CLD, and that, in CLD, IL-6 may be produced by cells within the air spaces.

Topics: Bronchoalveolar Lavage Fluid; Bronchopulmonary Dysplasia; Case-Control Studies; Female; Gestational Age; Humans; Immunohistochemistry; Infant, Newborn; Infant, Premature, Diseases; Interleukin-1; Interleukin-6; Interleukin-8; Male; Polymerase Chain Reaction; Transcription, Genetic

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

1. Infection in the neonatal period is difficult to diagnose and is a significant cause of morbidity and mortality in preterm infants. 2. We investigated prospectively the predictive value of plasma measurement of bacterial endotoxin (lipopolysaccharide), tumour necrosis factor-alpha, interleukin-6, interleukin-8, intercellular adhesion molecule-1 and C-reactive protein in 60 consecutive newborn infants suspected of having neonatal infection. Plasma samples were taken at the time of acute clinical deterioration. Sixty-two cord blood samples were studied as controls taken at elective Caesarean section. 3. Forty-three infants had confirmed infections, 25 with positive blood cultures. Tumour necrosis factor-alpha and bacterial endotoxin levels were not significantly elevated over controls, whereas interleukin-6, interleukin-8 and intercellular adhesion molecule-1 levels were all significantly increased in the infected group compared with controls (all P < 0.001). 4. Increased plasma intercellular adhesion molecule-1 levels were a highly sensitive (88%) indicator of clinical infection and were independent of C-reactive protein. Use of these two assays in combination improved the diagnostic sensitivity to 95% and gave a negative predictive value of 97%. addition of interleukin-6 or interleukin-8 measurements failed to further significantly enhance the prediction of infection. 5. Measurement of intercellular adhesion molecule-1 level may have a clinical role in rapidly confirming, or predicting, the likely diagnosis in cases of suspected neonatal infection.

Topics: Bacterial Infections; Biomarkers; C-Reactive Protein; Cesarean Section; Female; Fetal Blood; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; Lipopolysaccharides; Predictive Value of Tests; Pregnancy; Prospective Studies; Sensitivity and Specificity; Tumor Necrosis Factor-alpha

Topics: Dexamethasone; Exudates and Transudates; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Interleukin-8; Lung Diseases