interleukin-8 and Bronchiolitis--Viral

Respiratory syncytial virus (RSV) bronchiolitis in infancy is a major risk factor for recurrent wheezing and asthma. Because azithromycin attenuated neutrophilic airway inflammation in a murine viral bronchiolitis model, demonstration of similar effects in human subjects might provide a strategy for the prevention of postbronchiolitis recurrent wheezing.. We sought to investigate whether azithromycin treatment during RSV bronchiolitis reduces serum and nasal lavage IL-8 levels and the occurrence of postbronchiolitis recurrent wheezing.. We performed a randomized, double-masked, placebo-controlled proof-of-concept trial in 40 otherwise healthy infants hospitalized with RSV bronchiolitis who were treated with azithromycin or placebo for 14 days. IL-8 levels were measured in nasal lavage fluid and serum on randomization, day 8, and day 15 (nasal lavage only). The occurrence of wheezing episodes was assessed monthly over the ensuing 50 weeks.. Compared with placebo, azithromycin treatment did not reduce serum IL-8 levels at day 8 (P = .6) but resulted in a greater decrease in nasal lavage fluid IL-8 levels by day 15 (P = .03). Twenty-two percent of azithromycin-treated participants experienced at least 3 wheezing episodes compared with 50% of participants in the placebo group (P = .07). Azithromycin treatment resulted in prolonged time to the third wheezing episode (P = .048) and in fewer days with respiratory symptoms over the subsequent year in comparison with placebo (36.7 vs 70.1 days, P = .01).. In this proof-of-concept study azithromycin treatment during RSV bronchiolitis reduced upper airway IL-8 levels, prolonged the time to the third wheezing episode, and reduced overall respiratory morbidity over the subsequent year.

Topics: Azithromycin; Bronchiolitis, Viral; Disease Progression; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Interleukin-8; Male; Nasal Lavage Fluid; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Risk Factors; Treatment Outcome

Respiratory syncytial virus (RSV) bronchiolitis is the most common lower respiratory tract infection in infancy. To date, there is no effective therapy for RSV bronchiolitis. In order to investigate the efficacy of clarithromycin in the treatment of RSV bronchiolitis, the present authors conducted a randomised, double-blind, placebo-controlled trial comparing clarithromycin with placebo in 21 infants with a diagnosis of RSV bronchiolitis. The infants were randomised to receive clarithromycin or placebo daily for 3 weeks. Levels of interleukin (IL)-4, IL-8, eotaxin, and interferon-gamma were determined in plasma, before and after treatment, using ELISA. Six months after treatment, parents were surveyed as to whether their child had experienced wheezing within the previous 6 months. Treatment with clarithromycin was associated with a statistically significant reduction in the length of hospital stay, the duration of need for supplemental oxygen and the need for beta(2)-agonist treatment. There were significant decreases in plasma IL-4, IL-8 and eotaxin levels after 3 weeks of treatment with clarithromycin. Readmission to the hospital within 6 months after discharge was significantly lower in the clarithromycin group. In conclusion, clarithromycin has statistically significant effects on the clinical and laboratory findings in respiratory syncytial virus bronchiolitis. Therefore, clarithromycin treatment may be helpful in reducing the short-term effects of respiratory syncytial virus bronchiolitis.

Topics: Anti-Bacterial Agents; Bronchiolitis, Viral; Chemokine CCL11; Chemokines, CC; Clarithromycin; Double-Blind Method; Drug Administration Schedule; Female; Humans; Infant; Interferon-gamma; Interleukin-4; Interleukin-8; Length of Stay; Male; Respiratory Syncytial Virus Infections

The role of cellular immunity in disease severity in respiratory syncytial virus (RSV) bronchiolitis is largely unknown. This study investigated the association between disease severity and systemic cytokine responses in hospitalized ventilated and nonventilated RSV bronchiolitis patients. In whole blood cultures stimulated with phytohaemagglutinin (PHA), lymphoproliferative responses and interferon (IFN)-gamma and interleukin (IL)-4 production during acute illness were measured. In addition, plasma cytokines were measured. Measurements were repeated in the convalescent phase, 3-4 weeks after admission. Fifty patients were included. The median age in ventilaled patients was significantly lower than in nonventilated patients (1 versus 4 months, p<0.05). In comparison with nonventilated patients, the ventilated patients had significantly lower lymphoproliferative responses and a lower production of IFN-gamma and IL-4. In fact, IFN-gamma and IL-4 production in ventilated patients was almost completely undetectable. Plasma IL-8 levels in ventilated patients were significantly higher than in nonventilated patients. In the convalescent phase, lymphoproliferative and cytokine responses as well as plasma IL-8 levels were normal in both patient groups. Since RSV bronchiolitis is associated with the subsequent development of asthma, the possible skewing of the T-helper (Th1/Th2) cytokine balance was investigated. This was found neither in the acute nor in the convalescent phase. In conclusion, the data indicate that depressed lymphocyte function and elevated plasma interleukin-8 levels are markers of severe disease. It is suggested that age and maturation related immune mechanisms could explain the occurrence of severe respiratory syncytial virus bronchiolitis requiring mechanical ventilation in young infants.

Topics: Antibodies, Viral; Biomarkers; Bronchiolitis, Viral; Cells, Cultured; Female; Humans; Infant; Infant, Newborn; Interferon-gamma; Interleukin-12; Interleukin-4; Interleukin-8; Male; Phytohemagglutinins; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Severity of Illness Index; Th1 Cells; Th2 Cells

Maternally expressed gene 3 (MEG3), a long noncoding RNA (lncRNA) has been dysregulated in various tumors. However, the expression level and functional role of MEG3 in the progression of respiratory syncytial virus (RSV) infection remains to be elucidated. The present study quantified the expression level of MEG3 in the nasopharyngeal (NPA) samples of RSV‑infected patients and in BEAS‑2B cells infected with RSV. The findings of the present study demonstrated that the expression level of lncRNA MEG3 was reduced in the NPA samples of RSV‑infected patients and in BEAS‑2B cells infected with RSV. In vitro transfection revealed increased mRNA expression levels of toll‑like receptor 4 (TLR4), tumor necrosis factor‑α (TNFα) and interleukin (IL)‑8 following RSV infection in BEAS‑2B cells. Additionally, ectopic expression of MEG3 reduced the expression level of TLR4, subsequently suppressing the mRNA expression levels of TNFα and IL‑8, indicating the protective role of MEG3 in the process of RSV infection. It is of note, that RSV infection‑induced p38 mitogen activated protein kinase (MAPK) and nuclear factor‑κB (NF‑κB) activation was partly abolished by overexpression of MEG3. In conclusion, to the best of our knowledge, the present study provided the first evidence that lncRNA MEG3 expression level was reduced in the NPA samples of patients with RSV infection and RSV‑infected cells. Additionally, it was demonstrated that MEG3 protected human airway epithelial cells from RSV infection, primarily by suppressing TLR4‑dependent p38 MAPK and NF‑κB signaling.

Topics: Bronchiolitis, Viral; Cell Line; Child; Child, Preschool; Epithelial Cells; Female; Gene Expression Regulation; Host-Pathogen Interactions; Humans; Interleukin-8; Length of Stay; Male; Nasopharynx; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; RNA, Long Noncoding; Signal Transduction; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

Hospitalization with bronchiolitis is linked to the development of early childhood chronic wheeze and asthma. Viral etiology and severity of inflammation are potential contributing factors. Previously we observed reduced airway neutrophil infiltration in breastfed bronchiolitic infants, with a corresponding reduction in disease severity. This study aimed to examine whether respiratory viral etiology and co-infection alters the pattern of neutrophil influx, and the inflammatory mediator profile, resulting in epithelial damage in bronchiolitis.. Nasopharyngeal aspirates (NPAs) collected from hospitalized infants were assessed for viruses, soluble protein, cellular infiltrate, interleukin (IL)-6, -8, and myeloperoxidase (MPO).. NPAs were collected from 228 bronchiolitic and 14 non-bronchiolitic infants. In the bronchiolitic cohort, human rhinovirus was most prevalent (38%), followed by respiratory syncytial virus (36%), adenovirus (10%), and human metapneumovirus (6%), with 25% positive for viral co-infections and 25% negative for all screened viruses. Viral-induced bronchiolitis was associated with increased cellular infiltrate and protein, above control, and virus-negative infants (P < 0.05). Cellular infiltrate correlated to IL-6, -8, and MPO (r = 0.331, 0.669, and 0.661; P < 0.01). Protein, IL-6, -8, and MPO differed significantly between viral groups; however, the majority of marker values for all groups fall within an overlapping, indistinguishable range, precluding their use as biomarkers of viral etiology. No significant difference was found between single and viral co-infections for any parameter.. Bronchiolitic infants presenting with a detectable respiratory virus during hospitalization demonstrated elevated markers of airway tissue inflammation and injury. In this cohort, viral etiology did not discernibly modulate chemokine-mediated neutrophil infiltration and activation. Pediatr Pulmonol. 2017;52:238-246. © 2016 Wiley Periodicals, Inc.

Topics: Adenoviridae; Adenoviridae Infections; Breast Feeding; Bronchiolitis; Bronchiolitis, Viral; Coinfection; Female; Humans; Immunoassay; Infant; Inflammation; Interleukin-6; Interleukin-8; Male; Metapneumovirus; Nasopharynx; Neutrophil Infiltration; Neutrophils; Paramyxoviridae Infections; Peroxidase; Picornaviridae Infections; Polymerase Chain Reaction; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Rhinovirus; Severity of Illness Index

Clinical manifestations of acute bronchiolitis (AB) vary from minimal disease to severe respiratory failure. The response to respiratory viral infections is possibly influenced by genetic polymorphisms linked to the regulation of the inflammatory response. In the present study, we investigated whether interleukin-8 (IL-8) and interleukin-17 (IL-17) genetic variants are associated with the severity of AB. A group of Brazilian infants hospitalized with AB and a control group (infants with no or mild AB, without hospitalization) were genotyped for four IL-8/IL-17 variations. For replication, we studied an Argentinean population sample of infants with mild and severe AB. IL-8 polymorphism (rs 2227543) and IL-17 (rs2275913) variants showed significant associations with the severity of AB. The effect of the IL-8 variation could be replicated in the Argentinean sample. This finding suggests that IL-8 variations may influence the severity of AB in young infants. Further genetic association studies in low- or middle-income populations are necessary with the aim of expanding knowledge in this area.

Topics: Argentina; Brazil; Bronchiolitis, Viral; Case-Control Studies; Female; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Infant; Interleukin-17; Interleukin-8; Male; Polymorphism, Single Nucleotide; Severity of Illness Index

Topics: Azithromycin; Bronchiolitis, Viral; Female; Humans; Interleukin-8; Male; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human

Topics: Azithromycin; Bronchiolitis, Viral; Female; Humans; Interleukin-8; Male; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human

Current tools to predict the severity of respiratory syncytial virus (RSV) infection might be improved by including immunological parameters. We hypothesized that a combination of inflammatory markers would differentiate between severe and mild disease in RSV-infected children.. Blood and nasopharyngeal samples from 52 RSV-infected children were collected during acute infection and after recovery. Retrospectively, patients were categorized into three groups based on disease severity: mild (no supportive treatment), moderate (supplemental oxygen and/or nasogastric feeding), and severe (mechanical ventilation). Clinical data, number of flow-defined leukocyte subsets, and cytokine concentrations were compared.. Children with severe RSV infection were characterized by young age; lymphocytopenia; increased interleukin (IL)-8, granulocyte colony-stimulating factor (G-CSF), and IL-6 concentrations; and decreased chemokine (C-C motif) ligand (CCL-5) concentrations in plasma. The combination of plasma levels of IL-8 and CCL-5, and CD4+ T-cell counts, with cutoff values of 67 pg/ml, 13 ng/ml, and 2.3 × 10(6)/ml, respectively, discriminated severe from mild RSV infection with 82% sensitivity and 96% specificity.. This study demonstrates that the combination of CD4+ T-cell counts and IL-8 and CCL-5 plasma concentrations correlates with disease severity in RSV-infected children. In addition to clinical features, these immunological markers may be used to assess severity of RSV infection and guide clinical management.

Topics: Age Factors; Biomarkers; Bronchiolitis, Viral; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Chemokine CCL5; Chi-Square Distribution; Female; Humans; Infant; Infant, Newborn; Inflammation Mediators; Interleukin-8; Male; Predictive Value of Tests; Prognosis; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Retrospective Studies; Severity of Illness Index; Viral Load

Most patients with respiratory syncytial virus (RSV) bronchiolitis requiring admission to the pediatric intensive care unit (PICU) have no risk factors for severe disease. We sought to investigate the relationship between serum cytokine concentrations, innate immune responsiveness, and RSV disease severity.. Previously healthy infants (median age, 2.6 months) with RSV bronchiolitis (PICU, n = 20; floor, n = 46) and healthy matched controls (n = 14) were enrolled, and blood samples were obtained within 24 hours of admission to measure plasma tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), interleukin 8 (IL-8), and interleukin 10 (IL-10) concentrations and, whole blood lipopolysaccharide-stimulated cytokine production capacity.. Plasma IL-6, IL-8, and IL-10 concentrations were comparable between PICU and floor patients, but higher than in healthy controls (P < .05). In contrast, TNF-α, IL-6, and IL-8 production capacity was significantly decreased in PICU compared with both floor patients and healthy controls. In adjusted analyses, only impaired TNF-α and IL-8 production capacity were associated with longer length of stay (P = .035) and greater disease severity scores (P = .001).. Infants with severe RSV bronchiolitis had increased plasma cytokine concentrations and yet impaired innate immunity cytokine production capacity, which predicted worse disease outcomes. Immune monitoring of otherwise healthy infants with RSV lower respiratory tract infection could help identify patients at risk for severe disease at the time of hospitalization.

Topics: Bronchiolitis, Viral; Cytokines; Female; Humans; Immunity, Innate; Infant; Interleukin-6; Interleukin-8; Male; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Severity of Illness Index; Tumor Necrosis Factor-alpha

Decreased transplacental transfer of antibodies and altered immunoresponsiveness may place preterm (PT) infants at higher risk for serious consequences from respiratory syncytial virus (RSV) bronchiolitis. We hypothesize that among infants hospitalized with RSV bronchiolitis, immune response in PT infants may be different when compared with that of term infants. Nasal-wash samples were collected from 11 PT (<37 weeks of gestation) and 13 term infants (≥37 weeks of gestation) hospitalized with RSV bronchiolitis. Severity of illness (clinical score [CS]), admission peripheral oxygen saturation, and days subjects required supplemental oxygen were compared. Nasal-wash leukocyte count as well as cytokines for interleukin (IL)-8, IL-4, and interferon-γ (IFN-γ) were assayed. No significant differences in CS, admission SaO(2), and O(2) days were seen between PT and term infants. Nasal-wash leukocyte counts and IL-8 levels were higher in term infants compared with PT and correlated with severity (higher CS) in term (p < 0.05) but not in PT (p > 0.05) infants. IL-4 and IFN-γ levels did not differ between the 2 groups (p > 0.05). PT infants hospitalized with RSV bronchiolitis have lower nasal-wash leukocyte counts and a less robust IL-8 response than term infants, and only in term infants did IL-8 levels correlate with clinical disease severity.

Topics: Bronchiolitis, Viral; Cell Count; Cell Proliferation; Cells, Cultured; Disease Progression; Female; Hospitalization; Humans; Hyperbaric Oxygenation; Immunity, Cellular; Infant, Newborn; Interleukin-8; Leukocytes, Mononuclear; Nasal Mucosa; Oxygen Consumption; Pregnancy; Premature Birth; Respiratory Syncytial Viruses

To study the nutritional status of children with Respiratory Syncitial virus infection.. One hundred and twenty six children with acute respiratory infection, between the age of 4-24 months, were investigated for RSV infection with bronchiolitis, pneumonia and upper respiratory tract infection. Nasopharyngeal aspirates were collected and cytokine responses were determined by ELISA. Upper respiratory tract infections were detected in 16.66%, bronchiolitis in 30.15% and Pneumonia in 53.17% children.. Of the 126 patients, 46.66% children were positive for RSV while 58.33% were negative for RSV. Children with bronchiolitis were more commonly positive for RSV compared to URTI and pneumonia. RSV was almost equally distributed among boys (42.5%) and girls (48.7%). More children were RSV positive when the mean age lesser (8.4 mo) was compared to RSV negative (9.93 mo). Well nourished children and children with normal birth weight had more RSV positives, though not statistically significant. In a sub sample analysis of cytokines done (n=25), Interleukin-2 and Interleukin-8 levels were higher in the RSV positive children and these levels declined after 5 days of illness.. RSV is more commonly associated with bronchiolitis in younger infants with normal birth weight or more weight for age (WFA). Proinflammatory cytokine IL-8 was secreted at high concentrations in the nasopharyngeal aspirate in all the children.

Topics: Bronchiolitis, Viral; Child, Preschool; Female; Humans; India; Infant; Interleukin-2; Interleukin-8; Male; Nutritional Status; Pneumonia, Viral; Prevalence; Respiratory Syncytial Virus Infections; Respiratory Tract Infections; Risk Factors

To better understand the neutrophil activation and protease imbalance in respiratory syncytial virus (RSV) bronchiolitis.. Pediatric patients with RSV bronchiolitis were collected, 11 with the Lowell scores > or = 10 (severe group), and 19 with the Lowell scores < 10 (mild group). 20 RSV bronchiolitis patients in convalescent group, 24 patients with bacterial pneumonia, and 15 patients as control group. The percentages of neutrophils were detected. ELISA was used to detect the concentration of neutrophil elastase (NE) and interleukin (IL)-8, and the elastase inhibition capacity (EIC)/free neutrophil elastase activity were detected by colorimetry. Immunohistochemistry was used to examine the expression of alpha(1) antitrypsin (alpha(1)AT).. The neutrophil percentage, the NE and IL-8 concentration of the RSV bronchiolitis group (0.528, 6.39 x 10(7) kg/L and 13.62 x 10(9) kg/L)were all significantly higher than those of the control (0.074, 2.53 x 10(7) kg/L and 2.64 x 10(9) kg/L) and convalescent groups (0.306, 1.23 x 10(7) kg/L and 5.95 x 10(9) kg/L, all P < 0.05). The neutrophil percentage and IL-8 concentration of the convalescent group were both significantly higher than those of the control group (both P < 0.05). Increased expression of alpha(1)AT in RSV bronchiolitis was found when compared with convalescent infants (0.49 vs 0.09, P < 0.05). The free elastase activity level of the bronchiolitis group was 6/30, not different with 7/24 of pneumonia group, and it was only one in convalescent infants.. Mass of neutrophil aggregation and activation exist in RSV bronchiolitis, as well as protease system imbalance, and may play an important role in the inflammatory response and pathogenesis of RSV bronchiolitis.

Topics: alpha 1-Antitrypsin; Bronchiolitis, Viral; Humans; Infant; Interleukin-8; Leukocyte Elastase; Neutrophil Activation; Neutrophils; Respiratory Syncytial Virus Infections

Acute bronchiolitis is the main cause of emergency visits and hospitalizations in infants. Recent data suggest that neutrophil- and eosinophil-mediated inflammations were part of bronchiolitis pathophysiology. Apart from the defined risk factors, few was known on the underlying pathophysiology, which might point out the differences observed in the severity of the disease. The aim of this study was to assess whether the clinical severity of acute epidemic bronchiolitis in young infants might be related to a specific underlying inflammatory process. Total and differential cell counts, IL-8, eotaxin, eosinophil cationic protein (ECP) and albumin levels were assessed at the time of admission in bronchial secretions from 37 infants (median age 17 wk) with acute bronchiolitis. Outcome severity variables were: hypoxemia, Silverman score, tachypnea, feeding alteration, and duration of hospitalization. Neutrophils predominated, and eosinophils were present in 54% of the infants. IL-8 levels strongly correlated with ECP and albumin levels. Albumin levels were correlated with ECP and eotaxin levels. IL-8 levels were higher in infants with hypoxemia and inversely related with SaO(2) levels. IL-8 and albumin levels significantly rose with respiratory rate, and Silverman score. IL-8, albumin and ECP levels were significantly higher in infants hospitalized >/=7 days. Furthermore, IL-8 levels were correlated with the duration of hospitalization. Neither cell counts nor eotaxin levels were related to the severity criteria studied. This study suggests that IL-8-associated airway inflammation significantly contributed to the severity of acute epidemic bronchiolitis.

Topics: Acute Disease; Albumins; Biomarkers; Bronchiolitis, Viral; Disease Outbreaks; Enzyme-Linked Immunosorbent Assay; Eosinophils; Female; France; Humans; Hypoxia; Infant; Inflammation; Interleukin-8; Length of Stay; Leukocyte Count; Male; Neutrophils; Prospective Studies; Severity of Illness Index; Sputum

Topics: Acute Disease; Bronchiolitis, Viral; C-Reactive Protein; Humans; Infant, Newborn; Inflammation; Interferon-gamma; Interleukin-4; Interleukin-8; Leukocytes; Macrolides; Respiratory Syncytial Virus Infections; Treatment Outcome

Susceptibility to viral bronchiolitis, the commonest cause of infant admissions to hospital in the industrialised world, is associated with polymorphism at the IL8 locus. Here we map the genomic boundaries of the disease association by case-control analysis and TDT in 580 affected UK infants. Markers for association mapping were chosen after determining patterns of linkage disequilibrium across the surrounding region of chromosome 4q, a 550-kb segment containing nine genes, extending from AFP to PPBP. The region has three major clusters of high linkage disequilibrium and is notable for its low haplotypic diversity. We exclude adjacent chemokine genes as the cause of the association, and identify a disease-associated haplotype that spans a 250-kb region from AFM to IL8. In between these two genes there is only one structural feature of interest, a novel gene RASSF6, which is predicted to encode a Ras effector protein.

Topics: Base Sequence; Bronchiolitis, Viral; Case-Control Studies; Chromosome Mapping; Chromosomes, Human, Pair 4; Gene Frequency; Genes; Genetic Markers; Genetic Predisposition to Disease; Haplotypes; Humans; Infant; Interleukin-8; Linkage Disequilibrium; Polymorphism, Single Nucleotide; Respiratory Syncytial Virus Infections; United Kingdom; White People

The nature of the association between severe respiratory syncytial virus (RSV) bronchiolitis and subsequent wheezing remains unknown. In a previous study, we showed that genetic variation in the IL-8-promoter region is associated with susceptibility to severe bronchiolitis.. The purpose of this study was to assess the association between wheezing post-bronchiolitis and the genetic variant of IL-8 gene.. We collected data from 134 children who had suffered from bronchiolitis, enrolled in our previous study. The occurrence of wheezing post-bronchiolitis was recorded from a questionnaire sent by post. The association between the genotype and wheezing phenotype was assessed by family-based and case-control approaches.. Family-based association showed that the IL-8 variant was transmitted significantly more often than expected in the children who wheezed after the episode of bronchiolitis (transmission=56%, P=0.02). This effect was not observed in the group of children who had bronchiolitis but did not go on to wheeze. Moreover, the variant was significantly more frequent in post-bronchiolitis wheezers compared with the general population (odds ratio=1.6, 95% confidence interval 1.0-2.6).. These preliminary results suggest that there is a genetic predisposition to wheeze following severe RSV bronchiolitis.

Topics: Alleles; Bronchiolitis, Viral; Case-Control Studies; Chi-Square Distribution; Child; Female; Follow-Up Studies; Genetic Predisposition to Disease; Genotype; Humans; Interleukin-8; Male; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human

IL-8 is a strong inductor of inflammation. Accordingly, it plays a pivotal role in acute inflammatory responses during respiratory syncytial virus (RSV) infections and in chronic inflammatory diseases such as bronchial asthma and juvenile idiopathic arthritis. Recently, 2 studies have found association of the polymorphism -251A of IL8 with RSV bronchiolitis. Furthermore, epidemiologic studies have demonstrated an increased risk for the development of asthma after RSV bronchiolitis, and a common genetic background for the 2 diseases is currently being discussed.. This study investigated whether IL-8 is in association with asthma and/or arthritis and whether the results can confirm a common genetic background of RSV bronchiolitis and asthma.. The polymorphisms -A251T, C781T, C1633T, and A2767T within IL8 were genotyped in the following 4 populations: children with asthma, atopic children, children with juvenile idiopathic arthritis, and control subjects. Statistical analysis made use of the Armitage trend test and the software program Arlequine.. Association of all polymorphisms was found with asthma ( P =.008 to P =.03). Surprisingly -251T was associated with asthma, which is the opposite allele as described in association with RSV bronchiolitis. Furthermore, all polymorphisms were significantly more common in children with arthritis than in asthmatic children ( P =.006 to P =.02). No association was seen with the diagnosis of arthritis per se or with atopy.. This is the first study to describe association of IL-8 with asthma and a significant inverse distribution of the polymorphisms in juvenile idiopathic arthritis. In addition, the results of this study might suggest that RSV bronchiolitis and bronchial asthma have at least some different genetic factors.

Topics: Adolescent; Adult; Arthritis, Juvenile; Asthma; Bronchiolitis, Viral; Child; Child, Preschool; Genetic Predisposition to Disease; Genotype; Haplotypes; Humans; Interleukin-8; Polymorphism, Genetic; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human

This study measured chemokines in nasal lavage fluids (NLF) from infants with respiratory syncytial virus (RSV) bronchiolitis, defined by lung hyperinflation and wheezing. Comparison was made to RSV-positive infants without bronchiolitis and RSV-negative infants with acute respiratory illnesses. RSV-positive illnesses were associated with increased epithelial shedding, increased RANTES/protein ratios, and increased IL-8/protein ratios in NLF compared to RSV-negative illnesses. Among RSV-positive infants, bronchiolitics had greater total cell counts and percentage epithelial cells in NLF than nonbronchiolitics. Bronchiolitics also had roughly twice the NLF RANTES/IL-8 ratio than nonbronchiolitics (P =.043). Semiquantitative reverse transcriptase-polymerase chain reaction of nasal epithelium suggested similar RANTES/IL-8 ratio increases among bronchiolitics. A more mildly affected, RSV-positive outpatient population showed none of these differences. We conclude that RSV bronchiolitis is associated with a shift toward relatively more RANTES in nasal secretions of infants sick enough to require hospitalization, and mucosal epithelium may contribute to this process. Similar processes in the lower airways may enhance inflammation due to RANTES-responsive cell types and affect clinical manifestations.

Topics: Blood Proteins; Bronchiolitis, Viral; Chemokine CCL5; Eosinophil Granule Proteins; Epithelial Cells; Humans; Infant; Interleukin-8; Leukocyte Count; Leukocytes, Mononuclear; Nasal Lavage Fluid; Neutrophils; Outpatients; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Ribonucleases; RNA, Messenger

Large numbers of neutrophils in the airway of infants infected by respiratory syncytial virus (RSV) are recruited by chemokines, such as interleukin-8, and specific inflammatory molecules can delay apoptosis increasing their longevity. The aim of this study was to investigate whether airway secretions in RSV bronchiolitis contain factors that influence neutrophil apoptosis. Nasal lavage fluid (NLF) was obtained from 24 infants with RSV bronchiolitis (31 infant controls and 12 adults). Neutrophils isolated from healthy adult volunteers were incubated with the NLF in Dulbecco modified Eagle medium (DMEM) for 24 h, and apoptosis and necrosis were quantified using Hoechst 33342 and propidium iodide viability dyes. The presence of putative factors that delay neutrophil apoptosis was investigated using inhibitors to leukotriene-B4, lipopolysaccharide and the IL-8 receptor CXCR2, and blocking antibodies to granulocyte-monocyte colony-stimulating factor. Characterisation of NLF involved tests of thermal instability, proteolysis, deoxyribonuclease digestion and molecular filtration. NLF from infants with RSV bronchiolitis and controls significantly delayed neutrophil apoptosis, whereas NLF from healthy adults did not. None of these inhibitor molecules blocked this delay in apoptosis but activity was heat liable and >3 kDa. The study showed that nasal lavage fluid from infants significantly delays neutrophil apoptosis. The speculation is that the prolonged survival of neutrophils in the infant airway contributes to the characteristic accumulation of neutrophils in the airways of infants with respiratory infections.

Topics: Adult; Apoptosis; Bronchiolitis, Viral; Cell Survival; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Infant; Interleukin-8; Leukotriene B4; Nasal Lavage Fluid; Neutrophils; Polymyxin B; Receptors, Interleukin-8B; Respiratory Syncytial Virus Infections; Respiratory System

The differences between respiratory syncytial virus (RSV) and influenza A virus (IFAV) in the pathogenesis of wheezing in young children have not been clearly defined. The aim of this study was to assess the contributions of RSV vs IFAV in the pathogenesis of upper airway inflammation in wheezy young children. We compared interleukin (IL)-6, IL-8, IL-11, and interferon-gamma (IFN-gamma) levels in nasopharyngeal aspirates (NPA) from non-asthmatic children with respiratory virus infections (RSV in 17 children and IFAV in 13 children), asthmatic children with viral infections (RSV in nine children, IFAV in 10 children), and 22 unaffected healthy children (controls). Levels of IL-11 in NPA from asthmatic children were significantly higher than those from non-asthmatic children with RSV infection, and RSV infection enhanced the IL-11 production in NPA significantly compared to IFAV infection. Nasopharyngeal epithelium from children with RSV infection secreted more IL-6 than that of children with IFAV infection. There was little difference in the IL-8 and IFN-gamma levels between asthmatic and non-asthmatic children with RSV or IFAV infection. In conclusion, asthma enhanced IL-11 production in RSV infection rather than IFAV infection in early childhood. There was a trend towards greater IL-6 production in RSV infection compared with IFAV infection.

Topics: Asthma; Biomarkers; Bronchiolitis, Viral; Child Welfare; Child, Preschool; Cytokines; Female; Humans; Infant; Infant Welfare; Influenza A virus; Influenza, Human; Inhalation; Interferon-gamma; Interleukin-11; Interleukin-6; Interleukin-8; Male; Nasopharynx; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Statistics as Topic

Topics: Animals; Bronchiolitis, Viral; Humans; Infant, Newborn; Interferon-gamma; Interleukin-8; Rats; Respiration, Artificial; Respiratory Syncytial Virus Infections

Interleukin-8 (IL8) is believed to play a role in the pathogenesis of bronchiolitis, a common viral disease of infancy, and a recent U.K. family study identified an association between this disease and the IL8-251A allele. In the present study we report data, from a different set of families, which replicate this finding; combined analysis of 194 nuclear families through use of the transmission/disequilibrium test gives P = .001. To explore the underlying genetic cause, we identified nine single-nucleotide polymorphisms (SNPs) in a 7.6-kb segment spanning the IL8 gene and its promoter region and used six of these SNPs to define the haplotypic structure of the IL8 locus. The IL8-251A allele resides on two haplotypes, only one of which is associated with disease, suggesting that this may not be the functional allele. Europeans show an unusual haplotype genealogy that is dominated by two common haplotypes differing at multiple sites, whereas Africans have much greater haplotypic diversity. These marked haplotype-frequency differences give an F(ST) of.25, and, in the European sample, both Tajima's D statistic (D = 2.58, P = .007) and the Hudson/Kreitman/Aguade test (chi(2) = 4.9, P = .03) reject neutral equilibrium, suggesting that selective pressure may have acted on this locus.

Topics: Africa; Alleles; Animals; Bronchiolitis, Viral; Gene Frequency; Genetic Predisposition to Disease; Genetic Variation; Haplotypes; Humans; Infant; Interleukin-8; Introns; Molecular Sequence Data; Mutation; Pan troglodytes; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Prospective Studies; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Selection, Genetic; United Kingdom

The aim of this study was to determine whether interleukin (IL)-8 is released within the upper respiratory tract of infants during respiratory syncytial virus (RSV) bronchiolitis and whether the large number of polymorphonuclear neutrophils (PMNs) present in the respiratory tract of these infants are contributing to the inflammation through release of inflammatory mediators. Twenty-seven infants with acute bronchiolitis were recruited during one winter epidemic and 20 infant control subjects were recruited from a cohort participating in a community-based vaccine study. Samples of airways fluid were obtained using nasal lavage. The lavage fluid was spun to remove the cells, and the supernatant was stored at -70 degrees C. The supernatants were subsequently assayed for the presence of IL-8, total human neutrophil elastase (HNE) and neutrophil elastase activity. In the children with bronchiolitis compared with control infants, elevated levels of IL-8 (median (range) 1.53 (0-153) versus 0 (0-5.6) ng x mL(-1)) HNE (136 (32-694) versus 14 (0-516) ng x mL(-1)) and elastase activity (4 (1-220) versus 1 (0-339) mU x mL(-1)) were found. These results indicate that interleukin-8 is released in the upper respiratory tract in response to respiratory syncytial virus infection and suggest that polymorphonuclear neutrophil products are playing an important role in the inflammatory response to respiratory syncytial virus infection in infants with acute bronchiolitis. This contrasts with the predominantly eosinophilic response evident in atopic upper and lower respiratory tract disease.

Topics: Acute Disease; Antibodies, Viral; Biomarkers; Bronchiolitis, Viral; Humans; Infant; Infant, Newborn; Interleukin-8; Leukocyte Elastase; Nasal Lavage Fluid; Neutrophils; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Respiratory System; Retrospective Studies; Severity of Illness Index

Topics: Bronchiolitis, Viral; Humans; Infant; Interleukin-8; Respiratory Syncytial Virus Infections; Tumor Necrosis Factor-alpha