Low levels of interferon‐γ in nasal fluid accompany raised levels of T‐helper 2 cytokines in children with ongoing allergic rhinitis

The T‐helper 2 (Th2) cytokines interleukin‐(IL‐) 4, IL‐5, IL‐6, IL‐10 and the Th1 cytokine IFN‐γ and their associations with eosinophils, eosinophilic cationic protein (ECP) and immunoglobulin (Ig) E were studied in nasal lavage fluid from 60 school children with allergic seasonal rhinitis and 36 nonatopic healthy controls, before and during the pollen season. Eosinophil differential counts and IgE increased significantly in the patients during the pollen season. The eosinophil differential counts, ECP and IgE were all significantly higher during the season than in specimens simultaneously obtained from the nonatopic controls. Before season, the levels of ECP and IgE, but not eosinophils, were significantly higher in the patients than in the controls. During the season the nasal lavage fluid levels of IFN‐γ were significantly lower and the IL‐4/IFN‐γ quotients significantly higher in the allergic than in the control children. In the allergic children, but not in the controls, the nasal fluid levels of the Th2 cytokines IL‐4, IL‐5 and IL‐10 increased during the season, and together with IL‐6, were correlated with the differential counts of eosinophils, and with the levels of ECP and IgE. These findings are compatible with the hypothesis that a deficient release of the Th1 cytokine IFN‐γ plays an important role in the pathogenesis of allergic inflammation. Regardless of whether the defective IFN‐γ secretion is primary or a consequence of suppression by other cytokines, it will in the atopic subjects enhance the release of Th2 cytokines, which in turn will facilitate the development of allergic inflammation.     

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.     

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.     

Expression of and responses to CD2 and CD3 in 18‐month‐old children with and without atopic dermatitis

We hypothesize that atopy is associated with a reduced T‐cell function early in life and an imbalance in cytokine production. The purpose of this study was to investigate the expression of and responses to CD2 and CD3 in children who did or did not develop atopic dermatitis early in life. The expression of CD2 and CD3 was analyzed by flow cytometry, and proliferation of CD2 and CD3 was studied by ³H‐thymidine incorporation in phytohaemagglutinin (PHA)‐ and anti‐CD3‐stimulated peripheral blood mononuclear cells (PBMC) of 18‐month‐old children, 25 with and 29 without atopic dermatitis. Exogenous interleukin (IL)‐2 was added to compensate for possible functional differences in accessory cells. Anti‐CD3‐induced secretion of IL‐4, IL‐5, IL‐6, IL‐10, IL‐13, and interferon‐γ (IFN‐γ) was analyzed by enzyme‐linked immunosorbent assay (ELISA). Atopy was associated with a low proportion of CD2⁺ lymphocytes. Responsiveness to PHA, which activates lymphocytes partly via the sheep erythrocyte receptor, CD2, was reduced in the allergic children. The anti‐CD3‐induced proliferation declined more rapidly with antibody dilution in the allergic than in the non‐allergic children. Atopic dermatitis was associated with high levels of anti‐CD3‐stimulated IL‐5 secretion. The IL‐4/IL‐10 and IL‐4/IFN‐γ ratios were higher in children with elevated total immunoglobulin E (IgE) levels. Skin prick test‐negative children with eczema produced higher levels of IL‐10 than skin prick test‐positive children. In conclusion, atopic children have a reduced T‐cell function. Atopic dermatitis is associated with increased IL‐5 production, while high total IgE levels are associated with high IL‐4/IFN‐γ and IL‐4/IL‐10 ratios.     

Enhanced expression of cytokines/chemokines in cerebrospinal fluids in mumps meningitis in children

Background: The mumps virus is frequently the causative agent in aseptic meningitis and mumps has still prevailed in Japan. We compared data obtained from patients with mumps meningitis and patients with aseptic meningitis caused by other viruses in order to identify mumps meningitis‐specific cytokine/chemokine alterations in cerebrospinal fluide (CSF). Methods: We elucidated the cytokine/chemokine network based on the cytokine/chemokine profiles in CSF from children with mumps meningitis and meningitis due to other viral infections using multiplex cytokine measurement. Seventeen cytokines/chemokines, namely interleukin (IL)‐1β, IL‐2, IL‐4, IL‐5, IL‐6, IL‐7, IL‐8, IL‐10, IL‐12 (p70), IL‐13, IL‐17, interferon (IFN)‐γ, tumor necrosis factor (TNF)‐α, granulocyte colony‐stimulating factor (G‐CSF), granulocyte monocyte colony‐stimulating factor (GM‐CSF), monocyte chemoattractant protein‐1 (MCP‐1) and macrophage inflammatory protein‐1β (MIP‐1β), were measured simultaneously in CSF supernatants from eight children with mumps meningitis, 11 children with other types of viral meningitis and eight children with fever without neurological complications such as convulsion. Results: We found that IL‐8, IL‐10, IL‐12, IL‐13 and IFN‐γ showed a statistically significant increase in CSF from mumps meningitis when compared to other types of viral meningitis and fever without neurological complications. Conclusion: Mumps meningitis may induce a distinct immunological response when compared with other types of viral meningitis.     

Maturation of cytokine‐producing capacity from birth to 1 yr of age

Little is known about the immunologic maturation in the early stages of life. The aim of this study was to investigate maturation of immune system from birth to 1 yr of age and to compare immune functions between mothers and their children. Also the effect of atopy to the immune responses of children was examined. Cord blood samples (n = 228) and peripheral blood samples of children (n = 200) and their mothers (n = 208) 1 yr after birth were collected. Whole blood samples were stimulated for 24 and 48 h with Staphylococcal enterotoxin B (SEB), lipopolysaccharide (LPS) and the combination of phorbol ester and ionomycin (P/I). Production of TNF‐α, IFN‐γ, IL‐5, IL‐8 and IL‐10 was determined using ELISA. Significant mother‐to‐child correlation was detected in cytokine‐producing capacity at the age of 1 yr. TNF‐α (P/I, SEB and LPS stimulation), IFN‐γ (P/I and SEB), IL‐5 (P/I and SEB) and IL‐10 (P/I, SEB and LPS) producing capacity increased from birth to 1 yr of age. In general, stimulated cytokine responses were higher in mothers’ than in children’s blood samples, except in the case of P/I and LPS‐stimulated IL‐8, which were highest at birth. Maternal inhalation atopy was associated with increased cord blood IL‐5 (24 and 48 h) and IL‐10 (48 h) production following P/I stimulation. Also children of food atopic mothers expressed elevated cord blood IL‐10 (48 h, P/I) responses and decreased IFN‐γ/IL‐5 ratio (24 h, P/I). In addition, the production of IFN‐γ (24 and 48 h, P/I) and the IFN‐γ/IL‐5 ratio (24 h and 48 h, P/I) at the age of 1 yr was lower among children with food atopic mothers. In conclusion, our results suggest that both adaptive and innate immune responses increase from birth to 1 yr of age, but are still weak in comparison to adult responses. Cytokine responses of children begin to correlate with those of their mothers during the first year of life. Although only few associations were observed between atopy and cytokine‐producing capacity, our results suggest that children of atopic mothers express T_h2‐polarized cytokine pattern.     

Low frequency of CD4+, but not CD8+, T cells expressing interferon‐γ is related to cow's milk allergy in infancy

Low interferon‐γ (IFN‐γ) and tumor necrosis factor‐α (TNF‐α) production in peripheral blood mononuclear cells (PBMC) from patients with atopic dermatitis and food allergy have been reported previously. However, it remains unclear whether the weak cytokine production is caused by the imbalance of specific T‐cell subsets or by dysregulation of T‐cell function. In the present study we investigated the intracellular expression of these cytokines at a single‐cell level to clarify the background of the disruption. Twelve of 27 breast‐fed infants (0.1–8.8 months of age) had challenge‐proven cow's milk allergy (CMA), and 15 infants were studied as a healthy control group. PBMC were stimulated with phorbol 12‐myristate 13‐acetate (PMA) and ionomycin. The frequencies of the cells expressing intracellular IL‐4, IFN‐γ, and TNF‐α were assessed using flow cytometry. In addition, at this time‐point leucocyte subsets from the milk of mothers of these infants were evaluated using light microscopy. A lower number of CD8⁺ T cells and the defective capability of CD4⁺ T cells to express IFN‐γ in infant's peripheral blood co‐existed with a lower number of macrophages in their mother's milk.     

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.     

Neonatal BCG vaccination induces IL‐10 production by CD4+ CD25+ T cells

Akkoc T, Aydogan M, Yildiz A, Karakoc‐Aydiner E, Eifan A, Keles S, Akin M, Kavuncuoglu S, Bahceciler NN, Barlan IB. Neonatal BCG vaccination induces IL‐10 production by CD4⁺ CD25⁺ T cells.
Pediatr Allergy Immunol 2010: 21: 1059–1063.
© 2010 John Wiley & Sons A/S To determine the optimal time of Bacillus Calmette–Guerin (BCG) vaccination for induction of Th1 immunity, we measured the interferon (IFN)‐γ and interleukin (IL)‐10 secretion in purified protein derivative (PPD)‐stimulated peripheral blood mononuclear cell (PBMC) cultures in newborns vaccinated at birth or 2nd month of life. Moreover, role of CD4⁺ CD25⁺ T cells was studied by depletion assay at 8th month. Nineteen term and healthy newborns were randomized into two groups: Group I composed of 10 newborns vaccinated with BCG at birth and the remaining 9 (group II) at 2nd month of life. PBMCs were isolated at birth, 2nd and 8th months of age, and PPD‐stimulated IL‐10, 5 and IFN‐γ secretion were assessed. The same measurements were repeated for IL‐10 and IFN‐γ after the depletion of CD4⁺ CD25⁺ T cells at the 8th month. Children vaccinated at birth demonstrated higher PPD‐stimulated IFN‐γ and IL‐10 levels at 2 months of age when compared to non‐vaccinated ones (p = 0.038 and p = 0.022, respectively), whereas at 8 months, no significant differences were detected between the two groups. Moreover, CD4⁺ CD25⁺‐depleted T‐cell cultures resulted in lower PPD‐stimulated IL‐10 levels in those vaccinated at birth when compared to non‐depleted condition at the 8th month (p < 0.001). BCG at birth upregulated PPD‐stimulated IFN‐γ secretion at the 2nd month and remained still detectable at 8 month after the vaccination, whereas those vaccinated at the 2nd month of life lacked that increase in IFN‐γ response at the same time‐point. Furthermore, depletion assays suggest that CD4⁺ CD25⁺ T cells are involved in PPD‐stimulated IL‐10 secretion in response to BCG vaccination.     

Glucocorticoids enhance interleukin‐4 production to neo‐antigen (hyaluronidase) in children immunocompromised with cytostatic drugs

Immunoglobulin E (IgE)‐mediated immediate‐type allergic reactions to hyaluronidase have been observed in children with central nervous system (CNS) tumors. Glucocorticoids, used as therapy for brain edema, are discussed controversially as T helper 2 (Th2) stimulatory factors. In this study we investigated the role of glucocorticoids on a Th2 cytokine‐promoting effect in children with CNS tumors. Peripheral blood mononuclear cells (PBMCs) from: 29 children suffering from malignant brain tumors, of whom 23 received short‐term glucocorticoid treatment (for 3–4 days) during the course of chemotherapy; 18 children with nephrotic syndrome or renal transplantation receiving long‐term glucocorticoid treatment; and 13 healthy children, were incubated with phytohemagglutinin (PHA) and/or anti‐CD28 monoclonal antibody (mAb) and, in a second approach, with hyaluronidase. The concentrations of Th cell‐mediated cytokines – interleukin (IL)‐4, IL‐10, and interferon‐γ (IFN‐γ) – were measured in supernatants. The IL‐4 production of PBMCs incubated with PHA/anti‐CD28 mAb from children with repeated co‐administration of glucocorticoids, hyaluronidase, and cytostatic drugs (median: 249.9 pg/ml; range: 234.4–261.7) was significantly higher (p < 0.0001) than IL‐4 production of PBMC from children of all the other groups (median: 86.18; range: 16.0–212.5). There was no significant difference in the levels of IL‐10 and IFN‐γ within the groups. PBMCs stimulated only with hyaluronidase failed to produce detectable levels of cytokines. The results of this study indicate that repeated co‐administration of glucocorticoids and hyaluronidase (a neo‐antigen) enhance IL‐4 production in vitro and thus may induce the production of specific IgE antibodies in children immunocompromised with cytostatic drugs. Hyaluronidase itself does not stimulate in vitro IL‐4 synthesis in PBMCs of children receiving cytostatic drugs.     

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.     

Visceral leishmaniasis in two patients with IL‐12p40 and IL‐12Rβ1 deficiencies

Mutations of the IL12B and IL12RB1 genes underlie the development of IL‐12 p40 and IL‐12Rβ1 deficiencies, respectively, both of which cause predisposition to infection with weakly virulent mycobacteria and Salmonella. Infections with other intramacrophagic organisms have only been rarely observed. We identified two patients with visceral leishmaniasis who had autosomal recessive IL‐12 p40 and IL‐12Rβ1 deficiencies, respectively. This finding demonstrates the importance of IFN‐γ immunity in the control of leishmaniasis. We also searched the literature for similar reports in patients with these and other primary immunodeficiencies.     

Nasopharyngeal aspirate cytokine levels 1 yr after severe respiratory syncytial virus infection

Respiratory syncytial virus (RSV) infection is an important cause of recurrent wheezing in infants. Nevertheless, the link between RSV infection and wheezing has yet to be elucidated at the molecular level. Here, we present a preliminary study on the evolution of the immune response in the respiratory tract at long‐term after RSV infection. Twenty‐seven immune mediators were profiled in nasopharyngeal aspirates (NPAs) obtained from 20 children hospitalized due to a severe infection by RSV at discharge from hospital and again 1 yr later. The same mediators were profiled in parallel in NPAs from 12 healthy controls. In the year following discharge, 85% (17/20) of children of the RSV group suffered at least one episode of wheezing documented by the pediatrician. On the contrary, wheezing episodes were observed only in 25% (3/12) of children in the control group. While most of the mediators profiled returned to normal levels by 1 yr after discharge from hospital, RSV children showed a persistent nasal hyper‐secretion of VEGF, G‐CSF, IL‐10, IL‐6, IFN‐γ, IL‐7 and IL‐13. In previous works VEGF, IL‐10 and IFN‐γ have been put in relation with the pathogenesis of post‐virus induced asthma. G‐CSF, IL‐6, IL‐7 and IL‐13 are increased in respiratory and plasma samples of asthmatic patients. Here, we evidence for the first time a persistent elevation of these mediators as late as 1 yr after severe RSV disease resolution, reinforcing their possible implication in the pathogenesis of wheezing.     

Tracheal aspirate gene expression in preterm newborns and development of bronchopulmonary dysplasia

Background: Bronchopulmonary dysplasia (BPD) occurs in association with prenatal conditions predisposing infants to inflammation and remodeling of the premature lungs. Because of the lack of useful biomarkers for BPD, the gene expression of tracheal aspirate fluid (TAF) cells in premature infants was analyzed. Methods: Of 148 consecutive patients, 26 preterm infants (gestational age <34 weeks) were enrolled, who underwent assisted ventilation at birth for respiratory failure. Patients with congenital disorders were excluded. Half of these infants developed BPD. Interleukin (IL)‐10, interferon (IFN)‐γ, transforming growth factor (TGF)‐β1, and platelet‐derived growth factor (PDGF)‐B mRNA of TAF cells were quantified on real‐time polymerase chain reaction. Results: IL‐10 (P < 0.01) and IFN‐γ (P= 0.03) but not TGF‐β1 or PDGF‐B mRNA levels at birth were higher in BPD than in non‐BPD infants. IL‐10 expression differentiated BPD with the highest sensitivity (92%) and specificity (77%). IL‐10 levels correlated with TGF‐β1 (P= 0.03) and IFN‐γ (P= 0.01), but not with PDGF‐B levels. When BPD infants were classified according to comorbidity (group 1, six patients who suffered respiratory distress syndrome [RDS] but not chorioamnionitis [CAM]; group 2, five patients who had CAM but not RDS), PDGF‐B levels were higher in group 2 (P= 0.01). High IL‐10 expression was selected as a risk factor for BPD in infants who had CAM but not RDS (P= 0.01), although prolonged oxygen therapy was the most sensitive indicator for BPD (P < 0.01) on multivariate analysis. Conclusions: High IL‐10 expression in TAF cells at birth could predict the evolution of BPD, but with less impact than oxygen requirement. PDGF might play a different role in the inflammatory process of premature lungs.     

Pathogenic functions and diagnostic utility of cytokines/chemokines in EHEC‐HUS

Hemolytic ? uremic syndrome (HUS) is a severe complication of infection by Shiga toxin (STx)‐producing enterohemorrhagic Escherichia coli. Hemolytic ? uremic syndrome is defined clinically as a triad of non‐immune microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injuries. Neurologic complications such as acute encephalopathy are also observed. In humans, endothelial cells, proximal tubular epithelial cells, mesangial cells, podocytes, intestinal epithelial cells, and monocytes / macrophages are susceptible to STx‐mediated injury. Shiga toxin induces the secretion of inflammatory cytokines and chemokines from susceptible cells, including tumor necrosis factor‐α interleukin (IL)‐1, IL‐6, and IL‐8. These cytokines and chemokines contribute to the pathogenesis of HUS and encephalopathy by enhancing STx‐induced cytotoxicity and inducing inflammatory cell infiltration. Serum cytokine/chemokine levels are therefore useful as indicators of disease activity and predictors of progression from acute kidney injury to chronic kidney disease. Anti‐inflammation therapy combined with apheresis to remove excessive cytokines / chemokines and methylprednisolone pulse therapy to suppress cytokine/chemokine production may be an effective treatment regimen for severe E. coli‐associated HUS. However, this regimen requires careful monitoring of potential side effects, such as infections, thrombus formation, and hypertension.     

Relationships among specific viral pathogens,virus‐induced interleukin‐8, and respiratory symptoms in infancy

Both virus‐mediated damage to airway tissues and induction of pro‐inflammatory cytokines such as interleukin‐8 (IL‐8) could contribute to symptom severity during viral respiratory infections in children. To test the hypothesis that IL‐8 contributes to the pathogenesis of respiratory symptoms during naturally acquired respiratory viral infections in children, nasal wash samples collected from infants with acute viral infections (n = 198) or from healthy uninfected infants (n = 31) were analysed for IL‐8. Nasal wash IL‐8 was positively related to age in uninfected children (r_s = 0.36, p < 0.05). Respiratory syncytial virus (RSV) infection caused more severe respiratory symptoms compared to infections with influenza A, parainfluenza viruses, or rhinoviruses. In addition, RSV, parainfluenza and rhinovirus infections increased levels of IL‐8 in nasal lavage fluid, and there were some differences in the ability of the viruses to induce IL‐8 production (RSV>influenza, p < 0.05). Finally, there were significant correlations between nasal wash IL‐8 levels and symptom scores during infections with rhinovirus (r_s = 0.56, p < 0.001) or influenza A (r_s = 0.45, p < 0.05), but not with parainfluenza virus or RSV. These findings provide evidence of a close relationship between the generation of IL‐8 and symptoms during acute community‐acquired infections with rhinovirus or influenza A. In contrast, for RSV and parainfluenza infections, factors in addition to IL‐8 production appear to contribute to the generation of clinical symptoms.     

Cytokines in human milk and late‐onset breast milk jaundice

Background: Maternal milk plays an important role in the development of late‐onset breast milk jaundice (BMJ), possibly due to the unique characteristics of breast milk. The aim of this study was to investigate whether there is a relation between cytokine concentrations in the milk of nursing mothers and BMJ. Methods: Breast milk samples were collected from breast‐feeding mothers of healthy full‐term neonates, 40 with BMJ and 40 without jaundice. Milk samples were taken between the second and the fourth postpartum week. The concentrations of interleukin (IL)‐1 β, IL‐6, IL‐8, IL‐10, and tumor necrosis factor‐α were measured by flow cytometric bead array. Results: There were significant differences between the study groups in terms of IL‐1 β concentrations (P= 0.013). Not statistically significant but similar trends were also seen for IL‐10 (P= 0.067) and tumor necrosis factor‐α (P= 0.053) concentrations. However, no significant differences were noted in IL‐6 (P= 0.174) and IL‐8 (P= 0.285) concentrations. Conclusions: IL‐1 β concentration seems to be increased in milk of mothers whose infants had BMJ. Although the effect of these cytokines on BMJ is unknown, it may cause prolonged jaundice via hepatic uptake, hepatic excretion, conjugation and intestinal absorption.     

Cytokine profile of food‐allergic post‐liver transplant children is identified by high levels of IL‐5 and low IL‐10 secretion from patients' peripheral blood mononuclear cells

Severe allergic reaction to food following liver transplantation is a well‐known phenomenon. However, the mechanisms underlying this phenomenon are not yet elucidated. This study aimed to reveal the nature of the immune response in post‐transplanted allergic patients and compare them to non‐allergic transplanted as well as allergic and non‐allergic control subjects, with focus on cytokine milieu. Post‐liver transplant patients with and without allergic reactions as well as food‐allergic but otherwise healthy and healthy non‐allergic control patients were recruited. We reviewed patient records and routine laboratory tests and assayed subjects' PBMCs, studying cytokine secretion profile in response to different stimuli. Post‐transplant patients with food allergy showed a unique cytokine profile in response to various stimuli, with extremely elevated IL‐5, low IL‐10 secretion, and somewhat higher IFN‐γ. T regulatory cell number was not significantly different among the groups of patients and controls. Immune response of food‐allergic post‐liver transplant patients is identified by a unique cytokine profile when compared to allergic but otherwise healthy individuals.     

Elevated serum interleukin‐7 level in idiopathic steroid‐sensitive nephrotic syndrome

Background: Several cytokines have a pathological association with idiopathic steroid‐sensitive nephrotic syndrome (ISSNS) in inducing proteinuria or regulating T cells. Because interleukin (IL)‐7 plays important roles in regulating T‐cell proliferation and sustaining naïve or memory T cells, IL‐7 is one of the candidate cytokines in the pathogenesis of ISSNS. Very little is known, however, about the association of IL‐7 with ISSNS. To clarify the IL‐7 dynamics in children with ISSNS, serum IL‐7 level was investigated, from the nephrotic phase before steroid treatment (STx; group A1) to the remission phase with STx (group A2) and without STx (group A3). Methods: Eighteen children with ISSNS were included in the present study. A total of 25 paired samples were analyzed for groups A1 and A2, and a total of 10 paired samples for groups A1, A2, and A3 due to recurrence. Two control groups (with normal urinalysis, group B; or with nephrotic syndrome other than ISSNS, group C), matched for age and gender, were also included. Serum cytokine level was measured on bead‐based assay. Results: Each serum IL‐7 level in groups A1 and A3 was higher than each serum IL‐7 level of groups C and B, respectively. The group A2 serum IL‐7 level was higher than that of group A1. There was no statistical significance of serum IL‐7 level between group A1 and group A3. Conclusion: Serum IL‐7 level was elevated in children with ISSNS regardless of the status of the disease. This brings us one step closer to a better understanding of the pathophysiology of ISSNS in children.