CpG-Motive im Mausmodell für allergisches Asthma – Einfluß immunstimulatorischer DNA-Sequenzen auf die Entwicklung der allergischen Sensibilisierung und bronchialen Hyperreagibilität

Die Prävalenz und Inzidenz allergischer Erkrankungen haben in den industrialisierten Ländern in den vergangenen Jahrzehnten stetig zugenommen. Für die Entwicklung des allergischen Phänotyps sind genetische und Umwelteinflüsse im weitesten Sinne verantwortlich. Die „Hygiene-Hypothese“ geht davon aus,...

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Bibliographic Details
Main Author: Liller, Julius Henrik
Contributors: Herz, Udo (PhD) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2005
Online Access:PDF Full Text
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The prevalence and incidence of allergic diseases in industrialized countries have constantly increased during the past decades. Genetic as well as environmental influences in general are responsible for the development of the allergic phenotype. The „hygiene hypothesis“ supports the assumption that microbial stimuli have an allergy-protective effect. Especially bacterial antigenes and bacterial DNA-sequences with a central unmethylated cytosine/guanine motive (CpG) have been shown to have an immunostimulatory effect in the sense of an anti-allergic immune response (Th1). The purpose of this study was to evaluate whether a CpG-allergen-adsorbate (ISS) has the potential to alter the allergic (Th2-) phenotype in the sense of Th1-protection. Therefore, we gradually developed a mouse-model that allows us to observe the ISS-effects on clinical and immunological parameters. In a prophylactic approach, where treatment happened before triggering allergy symptoms, ISS is able to reduce number of inflammatory and mucus producing goblet-cells, prevent bronchial hyperresponsiveness (AHR) and boost Th1-associated IgG2a antibodies. After triggering the symptoms the effectiveness of CpG-treatment could be verified in the sense of secondary prevention. The secretion of Th1 cytocine INF-γ has increased. In a therapeutical approach, which comes close to the situation of a patient with allergic asthma, ISS is able to suppress AHR and boost IgG2a levels. On the level of cytocines the change from Th2 to Th1 is not achieved. The results show that the ISS-adsorbat-immunotherapy is a promising approach for the treatment of allergic asthma even though the observed effects can’t be characterized as an isolated repression of Th2- by Th1-immune response. The desired Th1-effects rather seem to develop parallel to the established Th2-response. The introduced murine model for the first time presents the opportunity to survey immunostimulatory effects in an close-to-clinical situation and opens up new perspectives for exploring this innovative concept of therapy.