Abstracts (complete list) - Wissenschaft Online

Lilli Podola, Hans Jürgen Ahr, Hans-Werner Vohr
THE INDUCTION PHASE OF ALLERGIC ASTHMA INVESTIGATED
BY A SHORT-TERM MODEL IN BROWN NORWAY RATS
Dermal and bronchial sensitization represents an increasing clinical problem. Particularly
low-molecular weight molecules like isocyanides contribute to the development of
occupational respiratory lung disease.
Today pre-clinical studies for hazard identification of respiratory sensitisation are
performed by long lasting and labour extensive inhalation studies which are currently
based on biphasic study protocols, induction and challenge. As there are no validated
protocols up to now exposure time and quantity vary in respect to the experimental
design.
The goal of our studies is to tap initiating mechanisms from short-term treatments as a
tool for hazard identification. Therefore, our investigations concentrated upon the
induction period of experimental asthma. Female Brown Norway rats were used after
intra-tracheal application of test substances like TMA in a 4 day model. After application
on two consecutive days evaluation of different parameters in the lung and draining
lymph nodes were performed. To avoid pronounced influence by unspecific inflammation
concentrations of applicants were used at the threshold level of irritation as measured
by cytotoxic reactions in the lung. We focussed on cellular events and their regulatory
mechanisms rather than the critical analysis of breathing pattern, i.e. functional activity.
Surprisingly, cell counts of eosinophils, one end point very simple to determine in BALF,
turned out to be a reliable end point. This holds true for the detection of asthmato-genic
substances as well as the irritant SDS. However from the data obtained so far different
kinetics of parameters seem to indicate distinct disease pattern.
To further analyse specific activation special emphasis was put on the regulation of T
cell responses in the draining lymph nodes and lungs followed by in vitro studies of
specific cell proliferation and multiplex cytokine pattern.
It should be possible to use this model to investigate the influence of routes of
administration on the development of allergic asthma.