Interleukin 8 and granulocyte elastase α1 proteinase inhibitor complex in the tracheobronchial aspirate of infants with chronic lung disease following intra-uterine infection

In order to elucidate the role of interleukin 8 (IL-8) in the development of chronic lung disease (CLD) of neonates with intra-uterine infection, serial and simultaneous measurements of the concentration of IL-8 and granulocyte elastase α₁ proteinase inhibitor complex (E-α₁PI) in the tracheobronchial aspirate of low birth weight infants were conducted. Infants with a high serum IgM level at birth, and who subsequently developed CLD, showed significantly high concentrations of IL-8 and E-α₁PI in the first 48 h. It seemed that IL-8 stimulated neutrophils to release neutrophil enzymes which, in turn, caused the lung tissue injury, resulting in the development of CLD following intra-uterine infection.     

Interleukin‐6, interleukin‐8, interleukin‐11, and interferon‐γ levels in nasopharyngeal aspirates from wheezing children with respiratory syncytial virus or influenza A virus infection

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‐γ (IFN‐γ) 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‐γ 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.     

Interleukin 8 and granulocyte elastase α1 proteinase inhibitor complex in the tracheobronchial aspirate of infants with chronic lung disease following respiratory distress syndrome

In order to elucidate the role of interleukin 8 (IL-8) on the development of chronic lung disease (CLD) in neonates following an episode of respiratory distress syndrome (RDS), serial and simultaneous measurements of the concentration of IL-8 and granulocyte elastase α₁ proteinase inhibitor complex (E-α₁ PI) in the tracheobronchial aspirate of very low birthweight infants with RDS were conducted. The concentration of IL-8 and E-α₁ PI in infants with CLD was low in the first 48 h of life, but dramatically increased after 48 h. The concentration of IL-8 between 48 h of life and day 5 was significantly correlated to the fraction of inspired oxygen concentration (F₁o₂) within 48 h of age, but not to the mean airway pressure. Interleukin 8 seemed to stimulate neutrophils to release granulocyte elastase which, in turn, caused lung tissue injury, resulting in the development of CLD. It is suggested that high F₁o₂ is an important factor causing IL-8 production in the lung.     

High production of interleukin‐10 and interferon‐γ in influenza‐associated MERS in the early phase

Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) occurs in various diseases and pathologies, and the clinical symptoms are not consistent with the impaired region. The mechanism of the region specificity is unclear. We investigated the cytokine profiling in cerebrospinal fluid (CSF) and serum obtained from a child with MERS during influenza infection, and compared them with those of serious another serious type of influenza‐associated encephalopathy. There was no elevation of Interleukin (IL)‐1β, which induces convulsion. The inhibitory cytokines of IL‐10 and IFN‐γ were elevated in the early phase in CSF. Comparing them with other patients, the elevation of the cytokine levels were generally mild. Considering that the prognosis of this MERS case was favorable and high levels of inhibitory cytokines including IL‐10 and IFN‐γ might work to localize the lesion and to prevent sequelae.     

Chemotherapy and interferon‐α treatment of Erdheim–chester disease

Erdheim–Chester disease (ECD) is a rare non‐Langerhans cell histiocytosis of an unknown origin. The prognosis of ECD is variable, and it mainly depends on the involved anatomic sites. The treatment modalities have not been standardized. Interferon‐α (IFN) has been reported to be effective in the management of ECD. We report here on an uncommon case with ECD in a 17‐year‐old female who had multiple lesions in the whole body and she was treated with chemotherapy and IFN. She has remained disease‐free for 2 years after the completion of treatment. Pediatr Blood Cancer. 2010;55:745–747. © 2010 Wiley‐Liss, Inc.     

Determination of T‐cell subpopulations and intracellular cytokine production (interleukin‐2, interleukin‐4, and interferon‐γ) by cord blood T‐lymphocytes of neonates from atopic and non‐atopic parents

This report describes the results of a prospective study on immunological markers in cord blood for the prediction of allergic diseases in children. First we evaluated methodological aspects of the flow cytometric technique on cord blood cytokine measurements. Subsequently, the T‐cell subsets and percentage of cytokine‐producing cord blood T‐helper (Th) and T‐suppressor/cytotoxic lymphocytes of neonates from atopic and non‐atopic parents were compared. A group of 33 healthy, full‐term newborn infants of whom 23/33 were at risk for atopy (i.e. having at least one parent with one or more atopic symptoms and positive specific immunoglobulin E [IgE] to at least one common inhalant allergen) was studied. A flow cytometric technique was used to analyze cord blood T‐cell subsets and to determine the percentage of interleukin (IL)‐2‐, IL‐4‐, and interferon‐γ (IFN‐γ)‐producing cord blood Th and T‐suppressor/cytotoxic lymphocytes following stimulation with phorbol 12‐myristate 13‐acetate (PMA) and ionomycin. The percentage of CD3 (T lymphocytes), CD3⁺ CD4⁺ (Th lymphocytes), CD3⁺ CD8⁺ (T‐suppressor/cytotoxic lymphocytes), CD19⁺ (B lymphocytes), CD3⁺ CD4⁺ CD45RO⁺ (memory Th lymphocytes), and CD3⁺ CD4⁺ CD45RA⁺ (naive Th lymphocytes) cells was unrelated to parental atopic status. PMA stimulation augmented the percentage of IL‐2‐ and IFN‐γ‐producing Th and T‐suppressor/cytotoxic lymphocytes, whereas the number of IL‐4‐producing T lymphocytes remained very low or undetectable. No differences in the percentage of IL‐2‐, IL‐4‐ and IFN‐γ‐producing Th and T‐suppressor/cytotoxic lymphocytes were found between neonates from atopic and non‐atopic parents. These results will be re‐evaluated when the atopic status of the children at the age of 1 and 2 years can be assessed.     

Association of development of chronic lung disease of newborns with neonatal colonization of Ureaplasma and cord blood interleukin‐8 level

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

Relation between serum IL‐4, IL‐13 and IFN‐γ levels and recurrence of wheezing episodes in infants with acute bronchiolitis

Lower respiratory tract infections are the most important factors among various causes which trigger wheezing in the first year of life. The factors associated with episodic wheezing in children with acute bronchiolitis are still subjects of research. Infections, environmental factors, immunologic mechanisms are sorted as etiologic risk factors of episodic wheezing. We aimed to investigate the relationship between serum interleukin (IL)‐4, IL‐13 and γ‐interferon (IFN‐γ) levels and recurrence of wheezing episodes in infants with acute bronchiolitis. One hundred twenty infants between 3 and 36 months with acute bronchiolitis enrolled in the study. Personal histories, clinical and laboratory data of infants were recorded. The patients were followed for a year. Venous blood samples were obtained to determine serum IL‐4, IL‐13, and IFN‐γ levels during acute bronchiolitis episode. The number of wheezing episodes was significantly higher in infants with a positive family history of allergy. A statistically significant correlation was determined between serum IL‐13 levels of infants and number of wheezing episodes. High serum IL‐13 levels and a positive history of allergy may have important roles in the recurrence of acute bronchiolitis.     

Influence of smoking on human milk tumor necrosis factor‐α, interleukin‐1β, and soluble vascular cell adhesion molecule‐1 levels at postpartum seventh day

Background: The aim of this study was to investigate the effect of maternal smoking during pregnancy on human milk interleukin‐1β, tumor necrosis factor‐α (TNF‐α) and soluble vascular cell adhesion molecule‐1 levels at the postpartum seventh day. Methods: Forty‐four mothers (age range: 21–34 years) were enrolled in the study. Mothers were interviewed and classified according to their smoking status into one of two groups: the smoking mothers (n= 21) and the nonsmoking mothers (n= 23). Results: There were no significant differences between study groups with respect to human milk interleukin‐1β (P= 0.12) and soluble vascular cell adhesion molecule‐1 levels (P= 0.83). However, TNF‐α levels were found to be significantly lower in the smoking mothers compared with the controls (P= 0.002). Conclusion: This study shows that maternal smoking during pregnancy affects the levels of TNF‐α in milk. The protective effect of human milk against infections seems to be impaired in smoking mothers.     

The role of TNF‐α in eosinophilic inflammation associated with RSV bronchiolitis

Choi J, Callaway Z, Kim HB, Fujisawa T, Kim CK. The role of TNF‐α in eosinophilic inflammation associated with RSV bronchiolitis.
Pediatr Allergy Immunol 2010: 21: 474–479.
© 2009 John Wiley & Sons A/S The purpose of our study was to investigate whether tumor necrosis factor (TNF)‐α correlates with eosinophilic inflammation that occurs during a lower respiratory tract infection with the respiratory syncytial virus (RSV) in children. Sixty children with RSV bronchiolitis (RSV group) and 20 healthy children with no respiratory symptoms (Control group) were enrolled. We measured the nasal lavage fluid (NLF) Th2 cytokine (IL‐5), proinflammatory cytokine (TNF‐α, IL‐8), eosinophil‐active cytokine [granulocyte‐macrophage colony stimulating factor (GM‐CSF), IFN‐γ], and eosinophil‐active chemokine (eotaxin, regulated on activation normal T cell excreted and secreted) levels for both groups. We also measured serum eosinophil‐degranulation product (eosinophil‐derived neurotoxin; EDN, eosinophil cationic protein; ECP) levels from RSV group. TNF‐α, IL‐8, GM‐CSF, IFN‐γ, and eotaxin levels were significantly higher in the RSV group compared with the Control group. TNF‐α correlated with GM‐CSF (r = 0.87, p < 0.0001), IFN‐γ (r = 0.92, p < 0.0001), eotaxin (r = 0.64, p < 0.0001), and IL‐8 (r = 0.84, p < 0.0001). TNF‐α may have an important role in eosinophilic inflammation of airways in children with RSV bronchiolitis.     

Neurocognitive function in patients with β‐thalassemia major

Background: Children with β‐thalassemia major (β‐TM) have multiple risk factors for developing cognitive impairment. The aim of the present study was to evaluate cognitive function in patients with β‐TM. Methods: Twenty children with β‐TM were enrolled into the study and were compared with a control group consisting of 21 healthy children. All participants were evaluated with neuropsychological tests and event‐related potentials (ERP). Results: All of the participants had normal IQ scores, but the patient group had significantly lower full‐scale, performance, and verbal IQs compared with the control group (P < 0.05). The number of children with visuomotor dysfunction was higher in the patient group compared with the control group (P < 0.05). In the P300 test, the patient group had significantly prolonged N1, P2 and N2 latencies at the FZ, and a prolonged N1 latency at the Cz compared with the control group (P < 0.05). The patient group also had lower N1 and P3N4 amplitudes at the Fz, and lower N1, N1P2 and P3N4 amplitudes at the Cz when compared with the control group (P < 0.05). Mismatch negativity latency and duration were longer in the patient group (P < 0.05). Conclusions: Neuropsychological tests are safe, and reliable for the diagnosis of cognitive impairment in β‐TM patients, and the use of ERP may facilitate early diagnosis. The number of β‐TM patients in the present study was limited, however, and larger numbers of patients are required in further studies.     

Upregulation of α‐enolase in acute rejection of cardiac transplant in rat model: Implications for the secretion of interleukin‐17

Acute allograft rejection remains a major problem in solid organ transplantation. The enzyme α‐enolase has been shown to induce an immune response in cardiac transplantation. In this study, we investigated the role of α‐enolase in acute allograft rejection in a rat model of heart transplantation. Hearts from either (WF: RT1^u) or (Lew: RT1¹) rats were transplanted into (Lew: RT1¹) rats. No rejection occurred in the isograft group, for which the median survival time was >168 days, whereas the median survival time of the allograft group was significantly less at 10 ± 2.1 days (n = 8 per group, p < 0.001). Increased inflammation was observed in allografts, including increased α‐enolase expression and increased numbers of infiltrating CD4⁺ T cells (p < 0.05). By immunohistochemical staining, we confirmed that α‐enolase was expressed not only in myocardial cells but also in the infiltrating lymphocytes. However, on the fifth day after transplantation, α‐enolase expression was no longer observed in the lymphocytes (n = 3, p < 0.001). In contrast, no lymphocytes were found in isografts after transplantation (n = 3, p < 0.001). α‐enolase expression was increased in lymphocytes, which are implicated in the acute rejection of cardiac transplants. Intragraft α‐enolase inhibition may be useful as an adjuvant therapy to systemic immunosuppression in heart transplantation.