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Recent studies demonstrate reduced interferon-gamma (IFN-γ) secretion in neonates who became atopic later in life. The underlying pathomechanism is still unknown. We therefore examined the effects of bacterial products on neonatal IFN-γ production acting through different T-cell- or antigen- presenting-cell (APC)-stimulating mechanisms: cord-blood mononuclear cells (CBMC) were incubated with lipopolysaccharide (LPS), staphylococcal enterotoxin E (SEE), or a combination of both and restimulated with PMA and ionomycin. LPS and SEE as single stimuli induced IFN-γ production to the same extent in CBMC of neonates with high and low risk of atopy. In contrast, a combination of LPS and SEE had a multiplying effect on IFN-γ secretion only in CBMC of neonates with low risk of atopy. Phenotype analysis revealed that only memory T cells showed impaired IFN-γ synthesis (median 3.6% IFN-γ-producing cells vs 14.2% in controls; P < 0.01), whereas IFN-γ production by naive T cells did not differ in either group. Taken together, these results point to the existence of a disturbed function of costimulatory mechanisms in neonates at high risk of atopy, provoking reduced memory T-cell IFN-γ production. [ABSTRACT FROM AUTHOR]

Formaldehyde (FA), a common indoor air pollutant, has been associated with increased prevalence rates of asthmatic symptoms among exposed individuals in epidemiologic surveys. We studied the influence of FA exposure on inhalative allergic sensitization in the guinea pig. Three groups of guinea pigs (n = 12 each) were exposed to clean air or two different FA concentrations (0.13 and 0.25 ppm) over 5 consecutive days. Exposure was followed by inhalation of 0.5% ovalbumin (OA) as sensitizing allergen. Three weeks later, specific bronchial provocation with OA was performed with body plethysmographic measurement of compressed air (CA). Furthermore, specific anti-OA-IgGl (reaginic) antibodies were determined in serum. In a further six animals, the respiratory tract was examined histologically for signs of inflammation directly after the end of FA or clean air exposure. In the group exposed to 0.25 ppm FA, 10/12 animals were found to be sensitized to OA (positive reaction on specific provocation) vs. 3/12 animals in the control group (P < 0.01). Furthermore, CA measurements of specific bronchial provocation and serum anti-OA-antibodies were significantly higher in the 0.25 ppm FA group than in controls (CA 0.35 vs. 0.09 ml median, P<0.01; anti-OA-IgGl 13 vs. <10 EU median, P<0.05), indicating enhanced sensitization. In the group exposed to 0.13 ppm FA, no significant difference was found compared to the control group. There was no sign of inflammation of the lower airways in FA-exposed guinea pigs other than mucosal edema, which was discovered by morphometry. We conclude that short-term exposure to a low concentration of FA (0.25 ppm) can significantly enhance sensitization to inhaled allergens in the guinea pig. [ABSTRACT FROM AUTHOR]

To assess the relation among eosinophil-related variables in the peripheral blood, bronchial hyperreactivity, and the presence of atopic dermatitis in children aged 5-14 years, we studied 11 patients with atopic dermatitis alone, six with asthma and atopic dermatitis, 12 with asthma alone, and 12 healthy controls. Eosinophil counts, levels of eosinophil cationic protein, and the capacity of eosinophils to generate leukotriene (LT) C4, as well as bronchial hyperreactivity and a severity score for atopic dermatitis, were determined. Eosinophil variables were significantly higher in both patient groups with atopic dermatitis than in normal controls. In particular, ionophore A 23187 LTC4 generation was higher in patients with atopic dermatitis alone (median 82, range 25-273 ng/106 cells) and patients with combined asthma and atopic dermatitis (median 68, range 32-583 ng/106 cells) than in normal controls (median 9, range 1-67 ng/106 cells). However, there was no difference between the group of atopic dermatitis patients with asthma and without asthma. We conclude that eosinophil variables in the peripheral blood are mainly influenced by the presence of atopic dermatitis, and not the presence and the severity of asthma in patients with both asthma and atopic dermatitis. [ABSTRACT FROM AUTHOR]

Salivary SIgA antibodies against RS virus were studied in 105 children during the first year of life. The infants were divided into groups according to their risk of atopy. At birth 13 neonates showed measurable amounts of SIgA to RS virus. In another 26 children specific antibodies were detected but in concentrations too low for quantitative analysis. During the first year of life this increased to 29 antibody-positive Samples with measurable amounts of antibody and 39 with concentrations too low for quantitative determination. At this time 8 children of the high risk group had developed symptoms of allergy. None of these children had measurable amounts of SIgA anti-RSV in their saliva. In comparison, 10 of the remaining 26 high risk infants without symptoms of allergy did have such antibodies. Atopic infants had significantly more respiratory infections during the first year of life than nonatopic infants. The avidity of SIgA anti-RSV in neonatal samples was significantly higher than avidity determined in breast milk SIgA but comparable to the avidity of serum IgG. During the first year of life a continuing decrease of salivary SIgA avidity was observed. [ABSTRACT FROM AUTHOR]

Elevation of salivary SIgA-anti-casein has been shown to occur in newborn infants at risk of allergy. The present study was designed to follow 158 infants over 3 years to relate the onset of clinical disease to SIgA levels at birth. Newborn infants were divided into 3 groups according to their risk of allergy: Group I, (n = 62; no allergy risk); Group 11, (n = 30; low allergy risk); Group 111 (n = 66; high risk group). The groups were matched for smoking, social background, sex, and dietary habits of the patients. SIgA-anti-casein was determined by a direct ELISA. During the first year 59 infants developed atopic diseases (n = 37 of Groups I and 11; II = 22 of Group 111). After 3 years 37/61 infants of the high risk group had developed allergic symptoms. The frequency of atopic disease correlated with increased salivary antibody titers at birth (p < 0.05). 54% of infants with antibody titers > 250 EU/ml developed atopic symptoms at 1 year, 76% high risk infants with this titer developed atopic symptoms at 3 years of age. This study provides evidence that elevation of SIgA-anti-casein at birth not only reflects atopic risk as defined by cord blood IgE or family history, but correlates with the actual development of allergic disease during the first 3 years of life. [ABSTRACT FROM AUTHOR]

Passive smoking has been shown to cause increased incidence of lower respiratory tract infection and wheezing in young children and an inceased risk of childhood asthma. To evaluate possible influence of tobacco smoke on allergic bronchial sensitization we exposed guinea pigs to tobacco smoke in 3 concentrations of clean air (control group) for 8 h on 5 consecutive days (median plasma cotinine 5.0-25.4-87.2 ng/l). The animals were sensitized by repeated inhalation with ovalbumin. Histologic examination at the end of exposure revealed reactive epithelial hyperplasia and regenerative changes as well as inflammatory reaction mainly in the lung periphery, and histamine provocation showed increased bronchial reactivity at the end of tobacco smoke exposure. Sensitization was measured by specific bronchial provocation testing using body plethysmographic measurement of compressed air (CA) and specific anti-ovalbumin-antibodies of the IgGM1-subclass in the serum, measured by direct ELISA in ELISA units (EU). The group with the highest tobacco smoke exposure differed significantly in bronchial reactivity on specific bronchial provocation tests (p <0.005) compared with the control groups and showed elevated unspecific IgG1-antibody levels indicating enhanced sensitization. We conclude that intensive exposure to tobacco smoke over a short period of 5 d can enhance inhalational allergic sensitization in the guinea pig and might explain the increased incidence of respiratory allergies in child passive smokers. [ABSTRACT FROM AUTHOR]

Background Viral respiratory tract infections have been previously considered to be associated with induction of allergic sensitization. Objective and Methods In order to investigate this relationship in an animal model, guinea-pigs were inoculated intranasally with Parainfluenza-3-(PI-3) virus (n = 16) or virus-free culture medium (controls, n = 12), sensitized at day 4 with inhaled ovalbumin (OA) and challenged 3 weeks later with inhaled OA using specific bronchial provocation testing with body plethysmographic measurement of compressed air (CA). Furthermore, specific anti-OA-IgG1-antibodies in serum before challenge were determined by enzyme linked immunosorbent assay ( ELISA). For investigation of airway epithelium permeability horseradish peroxidase (HRP) was inhaled at day 4 after inoculation by six animals, and HRP serum concentrations were determined by a direct ELISA 30 min after inhalation. Results PI-3 infected animals were found to be significantly more sensitized to OA compared with controls, with higher CA values (P< 0.001) on specific bronchial provocation and with increased specific anti-OA-IgG1 titers. Serum-HRP concentrations were about 20 times higher in the infected animals compared with controls. PI-3 infected and sham-infected animals had comparable bronchial reactions on specific provocation with OA when sensitized systemically. Conclusions We conclude that viral respiratory tract infection with PI-3 virus enhances inhalative allergic sensitization in the guinea-pig. Increased mucosal permeability to antigens may be an important pathophysiological mechanism. [ABSTRACT FROM AUTHOR]

Two boys, aged three and seven years with immune thrombocytopenic purpura continued to show platelet counts below 20,000/mm³ inspite of treatment with high dose gammaglobulin and steroids. Alpha-2b-interferon injections were followed by normalisation of platelet counts in both patients. No side effects were seen. Alpha-interferon may be a safe and effective treatment for childhood-ITP. [ABSTRACT FROM AUTHOR]