Ontogeny of T-helper 1 and T-helper 2 cytokine production in childhood

Compared to adults, infants and young children demonstrate differences in their immune response, indicating that there is maturation or change over time and it is probable that this may be reflected in cytokine production. Cytokine responses have been demonstrated to be different in atopic and non-atopic individuals. In this study, we examined T-helper 1 (Th1) (interferon-γ[IFN-γ]) and T-helper 2 (Th2) (interleukin [IL]-4, IL-5, and IL-13) cytokine release from atopic and non-atopic children in response to the staphylococcal superantigen, staphylococcal enterotoxin B (SEB). In non-atopic and atopic children, IFN-γ, IL-4, and IL-5 release was significantly related to age. Non-atopic children younger than 2 years of age were found to have significantly reduced Th2 (IL-4, IL-5, and IL-13) responses when compared with older, non-atopic children. Atopic children had a reduced IFN-γ response when compared with non-atopics in early childhood; however, the decreased IFN-γ response seen in early childhood did not persist after 10 years. These age-related changes in cytokine production provide further support for the concept that cytokine deviations may determine the natural history of atopic disease during early childhood. In addition, the present study indicates the necessity of age-matched controls when examining children for both Th1 (IFN-γ) and Th2 (IL-4) cytokine release.     

Probiotics during weaning reduce the incidence of eczema

A reduced microbial load early in life has been suggested to be linked to the increasing prevalence of allergic diseases in the industrialized world. Some studies have indicated that probiotics may be effective in the prevention of eczema. In vitro studies indicate that probiotics have immunomodulatory effects. In the present study, we evaluated the effects of feeding Lactobacillus F19 during weaning on the incidence of eczema and Th1/Th2 balance. In a double-blind, placebo-controlled randomized intervention trial, infants were fed cereals with (n = 89) or without Lactobacillus F19 (n = 90) from 4 to 13 months of age. We assessed the cumulative incidence of eczema at 13 months of age. The ratio of interferon-γ (IFN-γ) to interleukin 4 (IL4) mRNA expression levels in polyclonally stimulated peripheral blood T cells was used as a proxy for immune balance. Total and specific IgE serum levels were also assessed. The cumulative incidence of eczema at 13 months was 11% (4–17%, 95% CI) and 22% (13–31%, 95% CI) in the probiotic and placebo groups, respectively (p < 0.05). The number needed to treat was 9 (6.5–11.5, 95% CI). At 13 months of age, the IFN-γ/IL4 mRNA ratio was higher in the probiotic compared with the placebo group (p < 0.05). In contrast, there were no differences between groups in serum concentrations of IgE. In summary, feeding Lactobacillus F19 during weaning could be an effective tool in the prevention of early manifestation of allergy, e.g., eczema. The higher Th1/Th2 ratio in the probiotic compared with the placebo group suggests enhancing effects of Lactobacillus F19 on the T cell-mediated immune response.     

mRNA expression of T-helper 1, T-helper 2 cytokines in autoimmune hepatitis in childhood

Background: In the pathology of autoimmune hepatitis the immunity mechanism of T-helper 1 (Th1) and Th2 cells was recently evaluated. The purpose of the present study was to measure the mRNA levels in peripheral mononuclear cells and serum cytokines obtained from children with autoimmune hepatitis for a better understanding of the mechanism.
Methods: Twenty-five patients with autoimmune hepatitis and seven controls were enrolled. mRNA levels in peripheral mononuclear cells and serum cytokines were measured using real-time polymerase chain reaction and immunoassay.
Results: Serum interferon-γ (IFN-γ) and interleukin-4 (IL-4) were rarely detected. In contrast the IFN-γ/β-actin mRNA levels were high.
Conclusion: Autoimmune hepatitis is a Th1-predominant state, therefore immune modulation therapies that target the control of Th1 cytokines should be used.     

In vitro cow's milk protein-specific inflammatory and regulatory cytokine responses in preterm infants with necrotizing enterocolitis and sepsis

Enteral feeding with cow's milk formula is associated with neonatal necrotizing enterocolitis (NEC) and sepsis. Dietary antigen sensitization may play a role in promoting and/or sustaining inflammation in both conditions. Aiming at investigating cow's milk protein (CMP)-specific cytokine responses in preterm infants with NEC and sepsis, 14 babies with NEC, 14 matched healthy controls, and 10 septic controls were recruited. Unstimulated and stimulated peripheral blood mononuclear cells (PBMCs) secreting IFN-γ, IL-4, IL-10, and TGF-β1 were counted by the single-cell enzyme-linked immunospot (ELISPOT) assay. During the acute phase of NEC, patients showed a general pattern of a high level of cytokine secretion both when unstimulated and stimulated by mitogen [phytohaemagglutinin (PHA)] and CMPs: beta-lactoglobulin (β-lg) and casein. These responses were more marked to β-lg for IFN-γ, IL-4, and IL-10 than TGF-β1. Cytokine responses in sepsis were lower than in NEC (lowest in healthy controls, with a minimal TGF-β1 response). At term, lower frequencies of cytokine-secreting cells were elicited than during the acute phase, except for TGF-β1 secreting cells, which increased at term (in response to PHA and CMPs) particularly following not only NEC but also sepsis.     

Interferon-gamma pretreatment of peripheral blood mononuclear cells partially restores defective cytokine production in children with atopic dermatitis

Interferon-gamma (IFN-γ) is considered an important determinant of the balance between T-helper type 1 and 2 cytokines and has been used experimentally for the treatment of atopic dermatitis. However, contrasting results have been reported relative to the Th-UTh-2 cytokine profile in atopic patients. In this study, we examined cytokine production by polyclonally activated peripheral blood mononuclear cells (PBMC) from children with atopic dermatitis, and assessed the influence of in vitro IFN-γ pretreatment on these cells. A fraction of PBMC isolated from children with severe atopic dermatitis, as well as from age-matched controls, was initially exposed to IFN-γ. After washing, both treated and untreated cells were then put into culture either alone or with the addition of phytohemagglutinin (PHA) or phorbol myristate acetate (PMA) plus ionomycin. IL-4, IL-5, IL-10 and IFN-γ production were measured in the supernatants using commercially available ELISAs. PBMC from atopic patients produced more IL-4 (P = 0.04) and IL-10 (P = 0.03) and less IFN-γ (P = 0.01) than controls, when stimulated with PHA. Interestingly, in PMA + ionomycin stimulated cultures, the atopic cytokine profile was different with more IL-5 (P = 0.0068) and less IFN-γ production (P = 0.00046) than the control group. When cells were pretreated with IFN-γ, there were no significant differences between patients and controls. PBMC from children with atopic dermatitis show alterations in cytokine production, compatible in general terms with the Th-l/ Th-2 model. Exposure of PBMC to IFN-γ before activation results in a reduction of these differences, so that cytokine production becomes similar in the atopic and normal groups.     

Allergen-induced cytokine secretion in atopic and non-atopic asthmatic children

Atopic asthma is characterized by excessive T helper 2 (Th2)-like immunity to allergens in the bronchial mucosa. The Th2-cytokine interleukin (IL)-4 induces IgE production, while the Th2-cytokine IL-5 promotes eosinophilic inflammation in the airways of asthmatics. Most asthmatics are atopic, but a subgroup is non-atopic. We hypothesize that allergen-induced Th2, particularly IL-5, responses can be observed in peripheral blood in both atopic and non-atopic asthmatic children but not in healthy control children. The aim of the present study was to determine IL-4, IL-5, IL-9, IL-10, IL-13 and IFN-γ secretion induced from peripheral blood mononuclear cells (PBMC) by a broad panel of inhalant allergens (timothy, cat, birch, dog and house dust mite) in asthmatic children with and without sensitization. The study included 13 atopic asthmatic, 5 non-atopic asthmatic, and 12 non-atopic non-asthmatic children. PBMC were stimulated with allergens and cytokine production was measured with enzyme-linked immunosorbent assay (ELISA). Higher levels of cat and dog antigen-induced IL-5 release were more commonly observed in both atopic and non-atopic asthmatics than in controls. Children with atopic, but not non-atopic, asthma produced higher levels of allergen-induced IL-4 and IL-9 than controls. Non-atopic asthmatics produced more IL-10 than atopic asthmatics after cat stimulation. High levels of eosinophilia-associated IL-5 responses are induced by cat and dog allergen in both atopic and non-atopic asthmatic children. The Th2 cytokines IL-4 and IL-9 were associated only with atopic asthma, probably due to their IgE-inducing properties.     

Early intervention with suplatast tosilate for prophylaxis of pediatric atopic asthma: A pilot study

The onset of asthma may be related to Th2 cytokine dominance at the time when food allergies occur several months after birth. This study investigated the effectiveness of early intervention with a Th2 cytokine inhibitor (suplatast tosilate) for prevention of asthma in infants with food allergies and atopic dermatitis. Suplatast tosilate dry syrup (6 mg/kg daily) or a histamine H₁-blocker (ketotifen fumarate dry syrup: 0.06 mg/kg daily) was administered randomly to 53 infants with atopic dermatitis caused by food allergies. The primary endpoints were the incidence of asthma and the time to the onset of wheezing. The peripheral blood Th1/Th2 ratio, total IgE level, and eosinophil count were measured before and after treatment. After 24 months of treatment, the prevalence of asthma was significantly lower in the suplatast group (20.8%) than in the ketotifen group (65.6%, p < 0.01). Additionally, the time from the start of treatment to the initial episode of wheezing for infants who developed asthma was significantly longer in the suplatast group than the ketotifen group (p < 0.01). Furthermore, the eosinophil count was significantly decreased by suplatast treatment (p < 0.05), and there was a significant difference between the suplatast and ketotifen groups with respect to both the eosinophil count (p < 0.01) and the Th1/Th2 ratio (p < 0.05). The results of the present pilot study suggest that suplatast tosilate is useful for the primary prevention of wheezing and asthma in children.     

Reduced IL-2-induced IL-12 responsiveness in atopic children

Atopy may be associated with a reduced T-cell function particularly regarding maturation of T helper 1 (Th1) responses. We hypothesized that atopic children may have a reduced capacity to up-regulate the β₂ subunit of the interleukin-12 (IL-12) receptor (IL-12Rβ₂, the signal-transducing component). The study included 38 children followed from birth to the age of 7 years. Twenty one had a cumulative history of atopic disease, whereas 17 had none. Sixteen out of 21 children also had atopic symptoms within the past year (current), out of whom 10 children had atopic airway symptoms. The expression of IL-12Rβ₂ mRNA was analyzed by quantitative real-time PCR and the secretion of interferon-γ (IFN-γ), IL-5 and IL-10 was assessed by enzyme-linked immunosorbent assay (ELISA). Children with current atopic airway symptoms and high levels of total IgE up-regulated IL-12Rβ₂ mRNA expression less than non-atopic children with low IgE levels after IL-2 stimulation. This was accompanied by a low IL-2- and IL-12-induced IFN-γ production, possibly reflecting the reduced capacity of atopic children to up-regulate the IL-12 receptor. As IL-2 is needed to initiate and sustain immune responses and IL-12 promotes Th1 responses, this may contribute to the Th2-skewed pattern in atopic children.     

Cytokine profiles in 1-yr-old very low-birth-weight infants after enteral glutamine supplementation in the neonatal period

In a previous study, we found that glutamine-enriched enteral nutrition in 102 very low-birth-weight (VLBW) infants decreased both the incidence of serious neonatal infections and atopic dermatitis during the first year of life. The aims of this follow-up study were to determine whether these beneficial effects are attended by changes in Th₁ and Th₂ cytokine profiles at age 1 yr. Furthermore, we studied changes in cytokine profiles during the first year of life in these VLBW infants. In total, 89 infants were eligible for the follow-up study (12 died, 1 exclusion due to a chromosomal abnormality). Th₁ (IFN-γ, TNF- α and IL-2) and Th₂ cytokine (IL-10, IL-5, and IL-4) profiles following in vitro whole blood stimulation were measured at 1 yr. Cytokine profiles were measured in 59/89 (66%) infants. Glutamine-enriched enteral nutrition in neonatal period did not influence cytokine profiles at 1 yr. Cytokine profiles were not different in infants with and without allergic or infectious diseases. The beneficial effect of glutamine-enriched enteral nutrition on the incidence of serious neonatal infections and atopic dermatitis during the first year of life is not related to changes in the Th₁ and Th₂ cytokine profiles. Both Th₁ and Th₂ cytokine profiles increased during the first year of life in this cohort of VLBW infants.     

Single-centre vs. population-based outcome data of extremely preterm infants at the limits of viability

Aim:  In response to the disappointing outcome data of the population-based EPICure study published in 2000, we compared the outcome of infants 22 0/7 to 25 6/7 weeks of gestational age (GA) in a single tertiary care centre 2000–2004 with that of EPICure.
Methods:  EPICure tools and definitions, including 30 months' Bayley Scales.
Results:  Of 83 infants <26 weeks born alive, more were admitted to intensive care – 82% vs. 68% (p  <  0.0001) – and more infants survived to discharge (57% vs. 26%, p <   0.0001; 69% vs. 39%, p  <  0.01, of those admitted to intensive care). More infants, as a percentage of live births, survived without severe (41%, 34/83 vs. 20%, 233/1185, p <   0.0001) or overall disability (22%, 18/83 vs. 13%, 155/1185, p  =  0.03). However, at the border of viability – GA 23 and 24 weeks – the rate of infants surviving without overall disability was not significantly higher (13%, 6/45 vs. 9%, 56/623).
Conclusion:  In infants <26 weeks of GA, increased rates of survival and survival without disability were observed in a single-centre inborn cohort born 5–8 years later than the EPICure cohort. This did not translate into increased survival without overall disability in infants of 23–24 weeks of GA.     

Comparison of cytokine responses in nasopharyngeal aspirates from children with viral lower respiratory tract infections

Aim: To determine whether nasopharyngeal aspirates (NPAs) cytokine response is different according to the causative viruses in children with lower respiratory tract infections (LRTI).
Methods: NPAs from 277 children with LRTI caused by respiratory virus were evaluated. Based on the proven viral agents, LRTI patients were divided into four groups. Levels of IL-4, IL-5 and IFN-γ were determined by ELISA.
Results: Patients with influenza virus infection demonstrated significantly lower IL-4 and IL-5 levels than those with other three groups. Patients with respiratory syncytial virus (RSV) infection showed an increase in production of IL-4 and IL-5, and a decrease in the IFN-γ level when compared to patients with influenza virus infection. Interestingly, a similar Th2 response was seen in patients with parainfluenza virus or adenovirus infection.
Conclusion: These results demonstrate that respiratory viruses can induce different local cytokine responses. However, Th2 biased responses are not unique for RSV but seem to be predominant in respiratory viruses of young children.     

Method of birth alters interferon-gamma and interleukin-12 production by cord blood mononuclear cells

Many uncertainties exist regarding the capability of cord blood mononuclear cells (CBMC) to produce cytokines. A number of conflicting reports led us to examine the effects of method of birth on CBMC production of interferon-gamma (IFN-γ), interleukin-4 (IL-4) and interleukin-12 (IL-12). While constitutive production of IL-4 was found in both vaginally and cesarean-delivered infants, constitutive IFN-γ or IL-12 production was found in neither. CBMC from vaginally delivered infants responded to stimulation with concanavalin A/phorbol 12-myristate 13-acetate (Con A/PMA), phytohemagglutinin (PHA), and lipopolysaccharide (LPS) with significantly higher levels of IFN-γ than CBMC from unlabored cesarean section (CS) infants. Production of IL-12 was increased in the vaginally delivered group in response to LPS and PHA but not to ConA/PMA. In contrast, mode of delivery was not associated with differences in IL-4 production. These results indicate that mode of delivery significantly alters the capability of CBMC to produce some cytokines and therefore should be taken into account in interpreting fetal/neonatal mononuclear cell function studies.     

Association of cord blood cytokine levels with wheezy infants in the first year of life

As antenatal environment may influence the development of atopy-predisposing immune response, cord blood cytokine productions may be an important predictor for wheezing. We investigated cord blood cytokines in a prospective birth cohort, intensively monitored for wheezy infant outcome at 1 yr. Cord blood serum samples from 269 children were assayed for interleukin (IL)-1β, -2, -4 to -8, -10, -12 (p70), -13, and -17, interferon-γ, tumor necrosis factor-α, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor (G-CSF), monocyte chemotactic protein-1, and macrophage inflammatory protein-1β. Associations between family histories, antenatal and perinatal factors, cord blood cytokine concentrations, and wheezy infant outcomes (wheezing more than two times) were analyzed. In cord blood sera from 269 children, there were associations between high levels of IL-6, -8 and G-CSF concentrations, and cesarean section. Data at 1 yr were obtained from 213 infants, including 33 wheezy infants. Risk of wheezing was related to gestational age, birth weight, cesarean section, and maternal eczema, but not to bacterial/viral infection during pregnancy, maternal asthma, maternal smoking, or paternal history. High level of cord blood IL-8 concentration had a significant association with wheezy infant outcomes at 1 yr (p = 0.025). By using multivariate logistic regression analysis, birth weight [odds ratio(OR) = 0.998, 95% confidence interval (CI) = 0.997–1.000] and maternal eczema (OR = 5.356, 95% CI = 1.340–21.41), but no other factors, were significant predictors of wheezy infants. Birth weight, gestational age, and maternal history were important risk factors for wheezing in the first year of life. Several cord blood cytokine productions were influenced by cesarean section, and IL-8 may be a predictor for recurrent wheezing at 1 yr.     

FcγRIIIa-V/F 158 polymorphism in Turkish children with asthma bronchiale and allergic rhinitis

Fc receptors (FcR) play an important role in immune regulation. This might be linked to the variability in immune response, therefore relating to the pathogenesis of atopic diseases. The aim of the present study was to evaluate the Fc γ RIIIa gene polymorphism in Turkish children with asthma and allergic rhinitis. The study included 364 atopic children (184 bronchial asthma, 180 allergic rhinitis) and 234 healthy subjects as the control group, aged between 5 to 16 years. Patients were recruited from outpatient clinics of allergy and general pediatric care. Plasma IgE concentrations were measured by immunoassays and skin prick test was done in children with atopic diseases. The Fc γ RIIIa gene polymorphism was determined using the polymerase chain reaction method. Distribution of V158V genotype was significantly different among patient groups compared to controls (for asthmatic children OR: 5.33, 95% CI: 2.80–10.23, p < 0.001; for allergic rhinitis OR: 3.25, 95% CI: 1.75–6.07, p = 0.001). Distribution of 158 V allele was significantly different among asthmatic children (OR: 2.20, 95% CI: 1.65–2.92, p < 0.001) and allergic rhinitis patients (OR: 1.77, 95% CI: 1.32–2.35, p < 0.001) compared to healthy controls. Our study shows that the V158V genotype in Fc γ RIIIa gene polymorphism may be a genetic risk factor for the development of atopic diseases.     

Epigenetic modulation at birth – altered DNA-methylation in white blood cells after Caesarean section

Aim:  Delivery by C-section (CS) has been associated with increased risk for allergy, diabetes and leukaemia. Whereas the underlying cause is unknown, epigenetic change of the genome has been suggested as a candidate molecular mechanism for perinatal contributions to later disease risk. We hypothesized that mode of delivery affects epigenetic activity in newborn infants.
Methods:  A total of 37 newborn infants were included. Spontaneous vaginal delivery (VD) occurred in 21, and 16 infants were delivered by elective CS. Blood was sampled from the umbilical cord and 3–5 days after birth. DNA-methylation was analyzed in leucocytes.
Results:  Infants born by CS exhibited higher DNA-methylation in leucocytes compared with that of those born by VD (p < 0.001). After VD, newborn infants exhibited stable levels of DNA-methylation, as evidenced by comparing cord blood values with those 3–5 days after birth (p = 0.55). On postnatal days 3–5, DNA-methylation had decreased in the CS group (p = 0.01) and was no longer significantly different from that of VD (p = 0.10).
Conclusion:  DNA-methylation is higher in infants delivered by CS than in infants vaginally born. Although currently unknown how gene expression is affected, or whether epigenetic differences related to mode of delivery are long-lasting, our findings open a new area of clinical research with potentially important public health implications.     

Mannose-binding lectin cord blood levels and respiratory symptoms during infancy: a prospective birth cohort study

Respiratory infections cause considerable morbidity during infancy. The impact of innate immunity mechanisms, such as mannose-binding lectin (MBL), on respiratory symptoms remains unclear. The aims of this study were to investigate whether cord blood MBL levels are associated with respiratory symptoms during infancy and to determine the relative contribution of MBL when compared with known risk factors. This is a prospective birth cohort study including 185 healthy term infants. MBL was measured in cord blood and categorized into tertiles. Frequency and severity of respiratory symptoms were assessed weekly until age one. Association with MBL levels was analysed using multivariable random effects Poisson regression. We observed a trend towards an increased incidence rate of severe respiratory symptoms in infants in the low MBL tertile when compared with infants in the middle MBL tertile [incidence rate ratio (IRR) = 1.59; 95% confidence interval (CI): 0.95–2.66; p = 0.076]. Surprisingly, infants in the high MBL tertile suffered significantly more from severe and total respiratory symptoms than infants in the middle MBL tertile (IRR = 1.97; 95% CI: 1.20–3.25; p = 0.008). This association was pronounced in infants of parents with asthma (IRR = 3.64; 95% CI: 1.47–9.02; p = 0.005). The relative risk associated with high MBL was similar to the risk associated with well-known risk factors such as maternal smoking or childcare. In conclusion the association between low MBL levels and increased susceptibility to common respiratory infections during infancy was weaker than that previously reported. Instead, high cord blood MBL levels may represent a so far unrecognized risk factor for respiratory morbidity in infants of asthmatic parents.     

Promoting shorter duration of ventilator treatment decreases the number of painful procedures in preterm infants

Aim:  To investigate whether promoting shorter ventilator treatment decreases the number of painful procedures and the use of analgesics in preterm infants.
Methods:  Retrospective patient chart review of all preterm infants in one Neonatal Intensive Care Unit (NICU) was carried out in 2000 (n = 240) and 2005 (n = 206). Between these cohorts, early nasal continuous positive airway pressure (nCPAP) application and early extubation policy were introduced.
Results:  Fewer infants were intubated (22 vs. 32%, p = 0.03), the duration of ventilator treatment decreased (6.7 SD 11.3 vs. 9.0 SD 11.1 days, p < 0.001) and nCPAP treatment became more common (41 vs. 25%, p < 0.001) in 2005 than in 2000. Similarly, the infants' exposure to painful procedures did not decrease significantly (61.9 SD 98.5 vs. 67.1 SD 104.3 procedures, p = 0.32) but the procedures related to respiratory support were fewer (45.2 SD 79.5 vs. 68.9 SD 91.1 procedures, p < 0.001) in 2005 than in 2000. In addition, the amount of pain medication used was significantly lower in 2005 than in 2000. One day on a ventilator included more painful procedures than a day on nCPAP (11.2 95% CI: 11.0–11.5 vs. 4.2 95% CI: 4.1–4.4 procedures, p < 0.001) during both study years.
Conclusion:  Early nCPAP and early extubation policies were successfully implemented in an NICU resulting in less invasive respiratory support. This was associated with fewer painful procedures and less pain medication in the preterm infants who required respiratory support. Despite this positive effect, the number of painful procedures in all preterm infants stayed at the same level. Our results provide further support for the use of nCPAP in preterm infants.     

Serum concentration of macrophage-derived chemokine may be a useful inflammatory marker for assessing severity of atopic dermatitis in infants and young children

Chemokines are responsible for the trafficking of leukocytes to sites of inflammation. Serum chemokine levels were previously shown to be increased in adult patients with atopic dermatitis (AD). We tested whether serum concentrations of chemokines, including macrophage-derived chemokine (MDC), thymus and activation-regulated chemokine (TARC), eotaxin (EOX), interferon gamma inducible protein 10 (IP-10) and monocyte chemotactic protein 1 (MCP-1), are useful inflammatory markers for assessing AD severity in infants and young children. To investigate this, we assessed the severity of AD clinically using the SCORing Atopic Dermatitis (SCORAD) index system. Serum chemokine concentrations were determined by sandwich enzyme immunoassay. Twenty AD patients with a median age of 2.1 years [interquartile range (IQR): 0.6–4.2] were recruited. Their SCORAD score was 23.5 (12.5–33.5). Serum concentrations of MDC, TARC, EOX, IP-10 and MCP-1 were 2551 (1978–3935), 1469 (1125–3070), 68 (57–85), 126 (101−226) and 518 (419–614) pg/ml, respectively. Serum MDC levels correlated with SCORAD (r = 0.608, p = 0.004) and its extent (r = 0.629, p = 0.003) and intensity (r = 0.557, p = 0.011) components. Serum TARC concentration showed weaker correlation with extent (r = 0.474, p = 0.035) and intensity (r = 0.465, p = 0.039) of skin involvement but not SCORAD. The median serum levels of MDC (3131 vs. 2394 pg/ml; p = 0.031) and EOX (80 vs. 61 pg/ml; p = 0.046) were also higher in children with moderate as compared with mild AD. The other chemokines did not correlate with AD severity. In conclusion, our results suggest that serum MDC concentration may be a useful inflammatory marker for assessing AD severity in infants and young children.     

Medical treatment reverses cytokine pattern in allergic and nonallergic chronic rhinosinusitis in asthmatic children

A Th2 cytokine pattern has recently been reported both in allergic and nonallergic chronic rhinosinusitis in asthmatic children. The aim of the study was to evaluate the cytokine pattern in chronic rhinosinusitis in allergic and nonallergic asthmatic children before and after medical treatment. Thirty asthmatic children were evaluated, 18 males and 12 females (mean age 9.1 years). Sixteen were allergic and 14 were nonallergic. All children were asthmatic and suffered from chronic rhinosinusitis, whose diagnosis was confirmed by endoscopy. All of them were treated with amoxicilline-clavulanate (20 mg/kg b.i.d.) and fluticasone propionate aqueous nasal spray (100 µg daily) for 14 days; a short course of oral corticosteroid was also prescribed (deflazacort 1 mg/kg daily for 2 days, 0.5 mg/kg daily for 4 days and 0.25 mg/kg daily for 4 days). Rhinosinusal lavage and nasal cytology were performed in all subjects before and after medical treatment. IL4 and IFNγ were measured by immunoassay and inflammatory cells were counted by conventional staining. Thirteen allergic children and 12 nonallergic children showed a negative endoscopy after the treatment. Allergic subjects showed a significant decrease of IL4 (p = 0.0002) and a significant increase of IFNγ (p = 0.03) after the treatment. Nonallergic children showed a significant decrease of IL4 (p = 0.0007) and a nonsignificant increase of IFNγ. A significant reduction of the inflammatory infiltrate was detected in all asthmatic children (p < 0.05). This study confirms a Th2 polarization in chronic rhinosinusitis both in allergic and nonallergic asthmatic children. Moreover, the medical treatment of chronic rhinosinusitis reversed the cytokine pattern from a Th2 towards a Th1 profile both in allergic and nonallergic children.     

Evaluation of an association between gastrointestinal symptoms and cytokine production against common dietary proteins in children with autism spectrum disorders

OBJECTIVE: To evaluate an association between cytokine production with common dietary proteins as a marker of non-allergic food hypersensitivity (NFH) and gastrointestinal (GI) symptoms in young children with autism spectrum disorders (ASD). STUDY DESIGN: Peripheral blood mononuclear cells (PBMCs) were obtained from 109 ASD children with or without GI symptoms (GI [+] ASD, N = 75 and GI (-) ASD, N = 34], from children with NFH (N = 15), and control subjects (N = 19). Diarrhea and constipation were the major GI symptoms. We measured production of type 1 T-helper cells (Th1), type 2 T-helper cells (Th2), and regulatory cytokines by PBMCs stimulated with whole cow's milk protein (CMP), its major components (casein, beta-lactoglobulin, and alpha-lactoalbumin), gliadin, and soy. RESULTS: PBMCs obtained from GI (+) ASD children produced more tumor necrosis factor-alpha (TNF-alpha)/interleukin-12 (IL-12) than those obtained from control subjects with CMP, beta-lactoglobulin, and alpha-lactoalbumin, irrespective of objective GI symptoms. They also produced more TNF-alpha with gliadin, which was more frequently observed in the group with loose stools. PBMCs obtained from GI (-) ASD children produced more TNF-alpha/IL-12 with CMP than those from control subjects, but not with beta-lactoglobulin, alpha-lactoalbumin, or gliadin. Cytokine production with casein and soy were unremarkable. CONCLUSION: A high prevalence of elevated TNF-alpha/IL-12 production by GI (+) ASD PBMCs with CMP and its major components indicates a role of NFH in GI symptoms observed in children with ASD.