以單分子IL-12核酸載體在過敏性氣喘的動物模式中進行基因治療
Date Issued
1999
Date
1999
Author(s)
蔡銘哲
DOI
882314B002220
Abstract
Bronchial asthma is characterized by
chronic inflammatory process in the
airways, which translates to bronchial
hyer-responsiveness clinically. The
preferential activation of type 2 helper
(Th2) cells play a key role in the
pathogenesis. Hence the treatment
modality aimed at reversing the Th2
response has been eagerly sought for.
Interleukin 12 (IL-12), a heterdimeric
cytokine, has been demonstrated to have
2
beneficial effect in animal models of
atopic asthma in terms of its effect to
inhibit antigen-induced airway
hyperresponsiveness, inflammation and
Th2 cytokine expression. Its potential
therapeutic use, however, is limited by the
short-lived effect of injected cytokine.
Therefore we try to establish an animal
model of atopic asthma on which efficacy
of IL-12 plasmid gene therapy can be
tested.
In this year’s project, we succeed in
establishing an animal model of atopic
asthma. The combination of intraperitoneal
and intra-tracheal route of OVA
administration makes a good model of
Th2 inflammation in the lung. The
cytokine profile in broncho-alveolar
lavage (BAL) was of Th2 in pattern.
There was eosinophilia in the BAL. The
serum IgE specific to OVA can be
demonstrated in animals. Unfortunately
we were not able to perform pulmonary
function test in this model since the only
pulmonary function machine in our
facility has too much dead space for such
a small animal to be tested.
On the other hand, we also intended to
determine to expression of introduced
plasmid in order to define the best route of
DNA delivery. The reporter gene
expression could be detected in the lung
and spleen in the IV group. However,
the intratracheal route was unsuccessful in
this experiment. The problem may lie in
the technical difficulties per se or the
methodology of detecting reporter gene’s
expression. Delivery of plasmid DNA
via nebulization is worth trying since it
may be superior to intratracheal route in
terms of fewer techniques required and
more economic and efficient if smaller
chamber is employed.
Publisher
臺北市：國立臺灣大學醫學院小兒科
Type
report
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