In recent decades, the prevalence of allergic diseases including bronchial asthma, hay fever and atopic dermatitis, has risen steadily in high-income countries. The underlying mechanisms for this phenomenon remain largely unknown. Since the natural mutation rate is low, altered environmental and lifestyle conditions are thought to play an important role. Epidemiological and clinical studies have provided indirect evidence that infections may prevent the development of atopy and atopic disease. This is referred to as the “hygiene hypothesis”. According to the hygiene hypothesis, viral and/or bacterial infections could inhibit the T-helper (Th)-2 immune response associated with atopic reactions by stimulating a Th-1 response involved in defence of bacterial infections and delayed-type hypersensitivity reactions. In particular, the prenatal period and early childhood are considered to be critical for the establishment and maintenance of a normal Th-1/Th-2 balance. On the other hand, several studies suggested that infections exacerbate established allergic diseases, e.g. bronchial asthma, airway hyperresponsiveness and atopic dermatitis. Therefore, viral and/or microbial infections and/or their products may have bidirectional effects on the development of allergy and asthma. This review will focus on recent findings related to the interaction between allergic disorders and infectious diseases, with the main emphasis on bacterial infections.
Most infections with respiratory viruses induce Th1 responses characterized by the generation of Th1 and CD8(+) T cells secreting IFN-gamma, which in turn have been shown to inhibit the development of Th2 cells. Therefore, it could be expected that respiratory viral infections mediate protection against asthma. However, the opposite seems to be true, because viral infections are often associated with the exacerbation of asthma. For this reason, we investigated what effect an influenza A (flu) virus infection has on the development of asthma. We found that flu infection 1, 3, 6, or 9 wk before allergen airway challenge resulted in a strong suppression of allergen-induced airway eosinophilia. This effect was associated with strongly reduced numbers of Th2 cells in the airways and was not observed in IFN-gamma- or IL-12 p35-deficient mice. Mice infected with flu virus and immunized with OVA showed decreased IL-5 and increased IFN-gamma, eotaxin/CC chemokine ligand (CCL)11, RANTES/CCL5, and monocyte chemoattractant protein-1/CCL2 levels in the bronchoalveolar lavage fluid, and increased airway hyperreactivity compared with OVA-immunized mice. These results suggest that the flu virus infection reduced airway eosinophilia by inducing Th1 responses, which lead to the inefficient recruitment of Th2 cells into the airways. However, OVA-specific IgE and IgG1 serum levels, blood eosinophilia, and goblet cell metaplasia in the lung were not reduced by the flu infection. Flu virus infection also directly induced AHR and goblet cell metaplasia. Taken together, our results show that flu virus infections can induce, exacerbate, and suppress features of asthmatic disease in mice.
It was the aim of this study to analyze the impact of maternal Th2 immune responses on onset and subsequent development of allergen-specific immunity and immediate-type hypersensitivity in early childhood. In a well characterized mouse model of Th2 immunity, BALB / c mice were sensitized to ovalbumin (OVA) before mating followed by allergen aerosol exposure during pregnancy. At the end of pregnancy mice developed allergen-specific Th2 / Th0 immunity and immediate-type hypersensitivity responses to OVA. T cells from these newborns, when restimulated with PMA / ionomycin, demonstrated a lowered capacity to produce IFN-γ. To assess whether prenatal allergen exposure favors postnatal onset of a Th2-type immune response, these offspring were immunized to a novel antigen by a single injection of β-lactoglobulin (BLG). In contrast to offspring from non-sensitized mothers, offspring from OVA-sensitized mice showed both higher anti-BLG immunoglobulin titers and higher frequencies of immediate-type skin test responses. Our data suggest that Th2 / Th0 immunity present during pregnancy has a decisive impact on shaping of the Th1 / Th2 T cell profile in the neonate. Furthermore, this effect favors the development of Th2 immune responses, when mice are exposed to a novel antigen during early childhood.
Elevated expression of matrix metalloproteinases (MMPs) is suggested to have tumor marker potential in various tumors. MMPs are capable of disintegrating the basement membrane, which is a main characteristic of tumor invasion. They are specifically inactivated by tissue inhibitors of metalloproteinases (TIMPs). Squamous cell carcinomas of the head and neck (SCCHN) are known to be highly invasive tumors with early locoregional metastatic spread.To investigate the tumor marker potential of MMPs in SCCHN, MMP-2, -3, -8, -9, -13 and TIMP-1 serum levels were determined in 73 patients and compared to 74 controls. A correlation with T- and N-status, UICC-staging and grading was performed. Additionally, the influence of inflammation on the MMP serum concentration was examined.Significant differences between patients with SCCHN and controls were seen for MMP-3, -8 and -9. A significant correlation was found between MMP-8 concentration and T-status, N-status and UICC-staging. No correlation with the grading of the tumor was observed. Inflammatory diseases did not affect MMP and TIMP levels significantly.Some MMPs are elevated in the serum of patients with SCCHN and especially MMP-8 showed interesting tumor marker potential.
Abstract Allergic asthma is characterized by airway hyperreactivity, inflammation, and a Th2-type cytokine profile favoring IgE production. Beneficial effects of TGF-β and conflicting results regarding the role of Th1 cytokines have been reported from murine asthma models. In this study, we examined the T cell as a target cell of TGF-β-mediated immune regulation in a mouse model of asthma. We demonstrate that impairment of TGF-β signaling in T cells of transgenic mice expressing a dominant-negative TGF-β type II receptor leads to a decrease in airway reactivity in a non-Ag-dependent model. Increased serum levels of IFN-γ can be detected in these animals. In contrast, after injection of OVA adsorbed to alum and challenge with OVA aerosol, transgenic animals show an increased airway reactivity and inflammation compared with those of wild-type animals. IL-13 levels in bronchoalveolar lavage fluid and serum as well as the number of inducible NO synthase-expressing cells in lung infiltrates were increased in transgenic animals. These results demonstrate an important role for TGF-β signaling in T cells in the regulation of airway responses and suggest that the beneficial effects observed for TGF-β in airway hyperreactivity and inflammation may be due to its regulatory effects on T cells.
This article was originally published online on 8 April 2015 Many hydrolyzed cow's milk (CM) formulas are available for avoidance of allergic reactions in cow's milk allergic children and for prevention of allergy development in high risk infants. CM formulas were compared regarding the presence of immunoreactive CM components, IgE reactivity, allergenic activity, ability to induce T cell proliferation and allergic or pro-inflammatory cytokine secretion. Using biochemical techniques and antibody probes highly specific for seven different cow's milk allergens, a blinded analysis of a panel of eight cow's milk formulas, one non-hydrolyzed, two partially hydrolyzed, four extensively hydrolyzed and one amino acid formula, was conducted. IgE reactivity and allergenic activity of the formulas were tested with sera from cow's milk allergic patients (n=26) in RAST-based assays and with rat basophils transfected with the human FcεRI, respectively. Furthermore, the induction of T cell proliferation and the secretion of a panel of cytokines in PBMC cultures from cow's milk allergic patients and non-allergic individuals were assessed. Immune-reactive whey proteins (alpha-lactalbumin, beta-lactoglobulin) were found in the two partially hydrolyzed formulas and casein components in one of the extensively hydrolyzed formulas. One partially hydrolyzed formula and the extensively hydrolyzed formula containing casein components showed remaining IgE reactivity whereas the other hydrolyzed formulas lacked IgE reactivity. Interestingly, only two extensively hydrolyzed formulas and the amino acid formula did not induce T cell proliferation and pro-inflammatory cytokine release whereas the remaining formulas varied regarding the induction of Th2, Th1 and pro-inflammatory cytokines. The investigated CM formulas showed a great variability regarding the presence of immunogenic CM components, IgE reactivity, allergenic activity and induction of pro-inflammatory cytokines. These results of our study may explain different outcomes obtained in clinical studies using CM formulas for prevention and treatment and they show that certain CM formulas without allergenic and low pro-inflammatory properties can be identified.
for each drug for any change in indications and dosage and for added warnings and precautions.This is particularly important when the recommended agent is a new and/or infrequently employed drug.
