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Abstract
Severity and treatability of allergic airway inflammation persisting in the background of asthma may be influenced by the innate immunity. Exposure to lipopolysaccharide (Lps)—or other natural immune stimulatory agents—as well as pregnancy can induce the activation of innate immune processes. To further clarify the role of these factors the following examinations were performed:
In an experimental investigation, we have developed a model of eosinophil airway inflammation and airway hyper-responsiveness (AHR), which was induced by Lps and allergy together. Allergen challenge, preceded by Lps-priming resulted in more severe eosinophil inflammation and higher nitrite formation in sensitized BALB/c mice, than allergen provocation alone. After Lps priming, AHR and concentrations of Th2 cytokines in bronchoalveolar lavage fluid were decreased, but still remained significantly higher than in controls. Probably, some accessory—non-Th2—immune-mechanisms might have been activated by Lps, during the development of allergic inflammation. Eosinophil inflammation was partially, while nitrite production and AHR were observed to be largely dexamethasone resistant in Lps-primed allergized animals. Thus, an animal model of steroid-resistant asthma was established in mice. The role of inducible nitric oxide synthetase (iNOS) in AHR was also assessed. Our results demonstrated that 1400W—a selective inhibitor of iNOS—effectively and rapidly (within 2 hours) reversed AHR in allergized mice. This effect of 1400W was, however, absent after by Lps priming. In conclusion, Lps inhalation may exaggerate eosinophil inflammation and reduce responsiveness to anti-inflammatory treatment in allergic airway inflammation.
In our human study, the immunological interferences between asthma and pregnancy were examined. The IFN-γ+ and IL-4 + T cell counts—determined by flow cytometry—were markedly increased in peripheral blood of asthmatic pregnant women. Significant negative correlations were revealed between the sizes of these cell populations and maternal peak expiratory flow, as well as birth weight of their newborns. Thus, the culminating proliferation of IFN-γ+ and IL-4 + T lymphocytes may potentially impair fetal development as well as maternal airway symptoms.
