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Pneumologie 2000; 54(9): 412-418
DOI: 10.1055/s-2000-7185
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Georg Thieme Verlag Stuttgart · New York

Zur Immunpathogenese des Asthma bronchiale

S. Finotto, P. R. Galle, M. F. Neurath
  • Labor Immunologie I, Arbeitsgruppe mukosale Immunologie, I. Medizinische Klinik der Johannes Gutenberg Universität Mainz (Direktor: Univ. Prof. Dr. med. P. R. Galle)
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Publication History

Publication Date:
31 December 2000 (online)

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Zusammenfassung:

Asthma bronchiale ist eine Erkrankung des Respirationstraktes, die mit einer Entzündungsreaktion und Hyperreagibilität des Bronchialsystems gegenüber multiplen exogenen oder endogenen Stimuli assoziiert ist. Neuere Untersuchungen weisen auf die wichtige Rolle von proinflammatorischen Mediatoren und Zytokinen in der Pathogenese des Asthma bronchiale hin, die von Mastzellen, eosinophilen Granulozyten und T-Zellen produziert werden. Durch die verstärkte Expression proinflammatorischer Zytokine kommt es zu einer pulmonalen Entzündungsreaktion, die vor allem durch IL-4, IL-13 und IL-5 vermittelt wird. Aus den neuen Erkenntnissen über die Immunpathogenese des Asthma bronchiale in Tiermodellen hat sich eine Reihe innovativer Therapieansätze ergeben. Diese umfassen die Gabe rekombinanter antiinflammatorischer Zytokine (IL-10), die Wiederherstellung des lokalen Zytokingleichgewichts durch Gabe von TH1-induzierenden Zytokinen (IL-12), die Induktion von TGF-beta produzierenden Zellen und Inhibitoren von IgE sowie von proinflammatorischen Zytokinen (IL-4, IL-5) und deren Rezeptoren. Es ist zu erhoffen, dass es durch diese Behandlungsansätze gelingt, selektiver und effektiver in den Krankheitsverlauf eingreifen zu können, als dies bisher durch Gabe von Kortikosteroiden möglich ist. Der klinische Stellenwert der experimentellen Therapieansätze bleibt jedoch abzuwarten; insbesondere sind potenzielle Nebenwirkungen einer systemischen Behandlung mit pluripotenten rekombinanten Zytokinen und/oder Zytokinantagonisten zu untersuchen.

On the Immunopathology of Bronchial Asthma:

Allergic asthma is a chronic pulmonary disease associated with bronchoconstriction and inflammation. Recent studies have shown that mediator substances and proinflammatory cytokines produced by mast cells, eosinophils and T-lymphocytes appear to be important for the pathogenesis of asthma. These substances contribute both to the initiation and perpetuation of the disease. In particular, it has been shown that allergic asthma is associated with increased TH2 (IL-4, IL-5, IL-13) cytokine production that causes activation of eosinophils and T-cells and production of chemokines (e. g. eotaxin) by pulmonary fibroblasts. Based on recent advances in our understanding of the immunopathogenesis of asthma in animal models several novel therapeutic approaches have been developed. Such approaches comprise treatment with recombinant anti-inflammatory cytokines, treatment with TH1-inducing cytokines such as IL-12, induction of oral tolerance and TGF-beta producing T-cells that can provide bystander suppression for TH2 cells, inhibitors of IgE, and antagonists of proinflammatory cytokines (e. g. IL-4 and IL-5) and their receptors. These novel treatment modalities will hopefully permit a more selective and effective suppression of pulmonary inflammation and bronchoconstriction in patients with allergic asthma compared to local treatment with corticosteroids. However, the clinical value of these novel therapeutic approaches remains to be determined. In particular, long term efficacy and safety of immunomodulatory therapy has to be studied more in detail.

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Priv.-Doz. Dr. Dr. rer. nat S Finotto

I. Medizinische Klinik der Universität Mainz

Langenbeckstraße 1 55131 Mainz

Email: E-mail: finotto@mail.uni-mainz.de