Induction of oral tolerance with effects on numbers of IgE-carrying mast cells and on bystander suppression in young rats

The presence of IgE+ mast cells in the small intestine, bystander suppression of DTH and antibody responses to human serum albumin (HSA) were studied in young rats, made tolerant to ovalbumin (OA) by feeding an OA-containing diet for 1–4 weeks starting from weaning, and in sensitized control rats. One week after finishing the OA diet, both groups of rats were immunized with a mixture of OA and HSA in Freund’s complete adjuvant (FCA) at one site on the back. The animals were then colonized for 5 days with a genetically manipulated Escherichia coli producing OA. Immunohistochemical staining of the small intestine of the rats fed the OA diet for 4 weeks showed significantly fewer IgE+ mast cells in the lamina propria, a lower level of MHC class antigen was found in the epithelial cells and in the lamina propria, and the villus crypt depth was also significantly less in tolerant compared with sensitized rats (P<0.003, 0.007, 0.003, respectively). Sensitized rats showed a mild diarrhoea during the colonization in contrast to tolerant rats. All rats fed OA showed a significantly reduced IgE anti-OA antibody and DTH response to OA before colonization compared with the sensitized rats. Bystander suppression of IgG and IgE anti-HSA antibody responses was also seen, but only in the rats fed OA for either 1 or 4 weeks. Rats fed the OA-containing diet for 1, 3, or 4 weeks showed bystander suppression of the DTH response to HSA. After colonization with E. coli producing OA, rats tolerant to OA after either 1 or 4 weeks on an OA diet maintained tolerance to OA and bystander suppression HSA. These results suggest that oral tolerance to OA down-regulates signs of local inflammatory response by IgE, IgG antibody and T cell responses to OA, but also provides bystander suppression to an unrelated antigen, HSA

Different expression of IL-2 receptor α-chain on a lamina propria T cell population and goblet cells in rats orally tolerized or sensitized to ovalbumin (OA) after colonization with an OA-producing Escherichia coli

The aim of this study was to compare the local gut immune response in sensitized and orally tolerized experimental animals. The development of IgE/IgG antibodies and the DTH to OA was studied in rats made orally tolerant to OA and compared with sensitized control rats after colonization with an Escherichia coli genetically engineered to produce OA. At 3 weeks of age, pups were weaned onto a standard diet without OA or an OA-containing diet for 4 weeks and then switched to a standard diet without OA. Both groups of rats were parenterally immunized with a mixture of OA and human serum albumin (HSA) in Freund's complete adjuvant when they were 8 weeks old. After DTH measurement 2 weeks later, all rats were colonized with an E. coli producing OA for 5 days. The local immune response in the small intestine was assessed, using immunohistochemistry, as the expression of MHC class II molecules and IL-2 receptor (IL-2R) α-chain. The OA-tolerant rats showed the classical signs of oral tolerance, with a reduced IgE and IgG antibody and DTH response to OA before colonization. The difference between the two groups in the anti-OA antibody response became even more pronounced after colonization with the E. coli that produce OA. Rats orally tolerant to OA maintained a normal villus architecture after colonization, with a normal expression of MHC class II molecules similar to non-treated adult rats, but with a significantly higher (P = 0.004) expression of IL-2R α-chain on T cells in the lamina propria of the villus core compared with sensitized control rats. The tolerant rats showed a very weak staining with the anti-IL-2R α-chain-specific antibody on a few goblet cells in only one out of seven rats. In the sensitized control rats, a marked local immune response was seen with an intense staining with a monoclonal anti-IL-2R α-chain-specific antibody on goblet cells in five out of seven rats (P = 0.019) and also an increased expression of MHC class II molecules in the epithelial cells and cells in the lamina propria of all rats. Rats orally tolerant to OA maintained a normal villus architecture after colonization, but with a significantly higher (P = 0.004) expression of IL-2R α-chain on T cells in the lamina propria of the villus core compared with sensitized control rats. The novel finding that goblet cells express IL-2R α-chain and the striking difference in expression of the receptor and the numbers of goblet cells between tolerant and sensitized rats may suggest a direct T cell regulation of the goblet cells. A possibility that oral tolerance might be maintained by the activated T cells expressing IL-2R α-chain in the lamina propria of the villus core is also discussed

The risk of respiratory tract infections and antibiotic use in a general population and among people with asthma

Aim: The aim of this study was to investigate occupational, environmental, early life and other risk factors associated with respiratory infections and antibiotics use in a general population and among asthmatic individuals. Method: This study included 15842 participants of the Respiratory Health in Northern Europe (RHINE) study aged 25–54 years from five Nordic countries, who answered a questionnaire covering respiratory outcomes, exposures, demographic characteristics and numbers of infections and courses of antibiotics in the last 12 months. Multiple logistic regression with and without adjustment for age, sex, smoking status, body mass index and centre were used to study the risk of infection and antibiotics in relation to asthma, and also the association between infection and antibiotics and occupations. Results: In the whole population, 11.6% reported having three or more respiratory infections, and 14.7% had used antibiotics because of respiratory tract infections within the last year. Asthmatic participants reported tripled odds for such infections (adjusted OR 2.98, 95% CI 2.53–3.52) and antibiotics use (adjusted OR 3.67, 95% CI 3.18–4.24) as compared to non-asthmatic participants. Both in the general and the asthmatic population, female sex, obesity and exposure to building dampness were associated with respiratory infections. Female sex and current smoking and living in Tartu were associated with antibiotic use. The use of antibiotics was doubled in people hospitalised for severe respiratory infection in childhood. Conclusion: In this study we identified several factors associated with increased respiratory infections and use of antibiotics in a general population and among asthmatic individuals. The frequency of respiratory infections and subsequent antibiotic treatment were increased among those with asthma

The risk of respiratory tract infections and antibiotic use in a general population and among people with asthma

Aim The aim of this study was to investigate occupational, environmental, early life and other risk factors associated with respiratory infections and antibiotics use in a general population and among asthmatic individuals. Method This study included 15 842 participants of the Respiratory Health in Northern Europe (RHINE) study aged 25–54 years from five Nordic countries, who answered a questionnaire covering respiratory outcomes, exposures, demographic characteristics and numbers of infections and courses of antibiotics in the last 12 months. Multiple logistic regression with and without adjustment for age, sex, smoking status, body mass index and centre were used to study the risk of infection and antibiotics in relation to asthma, and also the association between infection and antibiotics and occupations. Results In the whole population, 11.6% reported having three or more respiratory infections, and 14.7% had used antibiotics because of respiratory tract infections within the last year. Asthmatic participants reported tripled odds for such infections (adjusted OR 2.98, 95% CI 2.53–3.52) and antibiotics use (adjusted OR 3.67, 95% CI 3.18–4.24) as compared to non-asthmatic participants. Both in the general and the asthmatic population, female sex, obesity and exposure to building dampness were associated with respiratory infections. Female sex and current smoking and living in Tartu were associated with antibiotic use. The use of antibiotics was doubled in people hospitalised for severe respiratory infection in childhood. Conclusion In this study we identified several factors associated with increased respiratory infections and use of antibiotics in a general population and among asthmatic individuals. The frequency of respiratory infections and subsequent antibiotic treatment were increased among those with asthma

Prevalence and incidence of respiratory symptoms in relation to indoor dampness: the RHINE study

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldBACKGROUND: An association between indoor dampness and respiratory symptoms has been reported, but dampness as a risk factor for the onset or remission of respiratory symptoms and asthma is not well documented. METHOD: This follow up study included 16 190 subjects from Iceland, Norway, Sweden, Denmark, and Estonia who had participated in the European Community Respiratory Health Survey (ECRHS I). Eight years later the same subjects answered a postal questionnaire that included questions on respiratory symptoms and indicators of indoor dampness. RESULTS: Subjects living in damp housing (18%) had a significantly (p<0.001) higher prevalence of wheeze (19.1% v 26.0%), nocturnal breathlessness (4.4% v 8.4%), nocturnal cough (27.2% v 36.5%), productive cough (16.6% v 22.3%) and asthma (6.0% v 7.7%). These associations remained significant after adjusting for possible confounders. Indoor dampness was a risk factor for onset of respiratory symptoms but not for asthma onset in the longitudinal analysis (OR 1.13, 95% CI 0.92 to 1.40). Remission of nocturnal symptoms was less common in damp homes (OR 0.84, 95% CI 0.73 to 0.97). CONCLUSIONS: Subjects living in damp housing had a higher prevalence of respiratory symptoms and asthma. Onset of respiratory symptoms was more common and remission of nocturnal respiratory symptoms was less common in subjects living in damp housing

Distribution and determinants of house dust mite allergens in Europe: The European Community Respiratory health survey II.

Background: Several studies in European homes have described allergen levels from the house dust mite species Dermatophagoides pteronyssinus and to a lesser extent Dermatophagoides farinae, but geographic comparisons of exposure levels and risk factors have been hampered by a lack of standardized methods. Objective: To study the distribution and determinants of the major house dust mite allergens Der p 1 and Der f 1 in 10 European countries using a common protocol. Methods: During home visits with 3580 participants of the European Community Respiratory Health Survey II from 22 study centers, mattress dust was sampled and analyzed for Der p 1, Der f 1, and Der 2 allergen. Information on housing characteristics was obtained by both observations and interview. Results: Der 1 and Der 2 allergens were detectable (&ge;0.1 &mu;g/g) in 68% and 53% of the samples, respectively. Large differences in allergen levels between study centers were observed, and geographic patterns for Der p 1 and Der f 1 were different. Low winter temperatures reduced Der p 1 rather than Der f 1. Important risk factors for high allergen levels included an older mattress, a lower floor level of the bedroom, limited ventilation of the bedroom, and dampness for Der p 1 but not for Der f 1. Conclusion: There are large qualitative and quantitative differences of house dust mite allergen levels in Europe, which can partly be explained by geographic and housing characteristics. Clinical implications: Mite allergen exposure may be reduced by replacing the mattress regularly and increasing ventilation of the bedroom, particularly in winter. &copy; 2006 American Academy of Allergy, Asthma and Immunology