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a Inflammation Research Unit,
School of Pathology, University of New South Wales, Sydney, Australia
2052, b Division of Biochemistry and Molecular Biology, John Curtin
School of Medical Research, Australian National University, Canberra,
Australia 0200
Correspondence to: Dr R K Kumar.
Received 10 February 1998; Returned to authors 8 April 1998; Revised version received 8 May 1998; Accepted for publication 2 June 1998
BACKGROUND
Existing murine models of asthma
lack many of the inflammatory and epithelial changes that are typical
of the human disease. Moreover, these models are frequently complicated
by allergic alveolitis.
METHODSHigh IgE responder BALB/c mice were
systemically sensitised to ovalbumin and chronically challenged with
low particle mass concentrations of aerosolised ovalbumin. Titres of
anti-ovalbumin IgE in serum were measured at two weekly intervals by
enzyme immunoassay, accumulation of inflammatory cells and
histopathological abnormalities of the epithelium were quantified
morphometrically in the trachea and the lungs, and airway reactivity
was assessed by measuring bronchoconstriction following intravenous
administration of methacholine.
RESULTSMice sensitised by two
intraperitoneal injections of ovalbumin developed high titres of IgE
antibodies to ovalbumin. Following exposure to low concentrations of
aerosolised antigen for up to eight weeks these animals developed a
progressive inflammatory response in the airways, characterised by the
presence of intraepithelial eosinophils and by infiltration of the
lamina propria with lymphoid/mononuclear cells, without associated
alveolitis. Goblet cell hyperplasia/metaplasia was induced in the
intrapulmonary airways, while epithelial thickening and subepithelial
fibrosis were evident following chronic exposure. In parallel, the mice
developed increased sensitivity to induction of bronchospasm, as well
as increased maximal reactivity. Non-immunised mice exposed to
aerosolised ovalbumin had low or absent anti-ovalbumin IgE and did not
exhibit inflammatory or epithelial changes, but developed airway hyperreactivity.
CONCLUSIONSThis experimental model
replicates many of the features of human asthma and should facilitate
studies of pathogenetic mechanisms and of potential therapeutic agents.
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