Title: Respiratory response to toluene diisocyanate depends on prior frequency and concentration of dermal sensitization in mice
Authors: Vanoirbeek, Jeroen ×
Tarkowski, Maciej
Ceuppens, Jan
Verbeken, Eric
Nemery, Benoit
Hoet, Peter #
Issue Date: Aug-2004
Publisher: Academic Press
Series Title: Toxicological Sciences vol:80 issue:2 pages:310-21
Abstract: Occupational asthma is the principal cause of work-related respiratory disease in the industrial world. In the absence of satisfactory models for predicting the potential of low molecular weight chemicals to cause asthma, we verified that dermal sensitization prior to intranasal challenge influences the respiratory response using toluene diisocyanate (TDI), a known respiratory sensitizer. BALB/c mice received TDI or vehicle (acetone/olive oil) on each ear on three consecutive days (days 1, 2, and 3; 0.3 or 3% TDI) or only once (day 1, 1% TDI). On day 7, the mice received similar dermal applications of vehicle or the same concentration of TDI as before ("boost"). On day 10, they received an intranasal dose of TDI (0.1%) or vehicle. Ventilatory function was monitored by whole body plethysmography for 40 min after intranasal application, and reactivity to inhaled methacholine was assessed 24 h later. Pulmonary inflammation was assessed by bronchoalveolar lavage and histology. Mice that received an intranasal dose of TDI without having received a prior dermal application of TDI did not exhibit any ventilatory response or inflammatory changes compared to vehicle controls. In contrast, mice that had received prior application(s) of TDI, even if only on day 7, exhibited the following: ventilatory responses, compatible with bronchoconstriction, immediately after intranasal application with TDI; enhanced methacholine responsiveness 24 h later; and pulmonary inflammation characterized by neutrophils. This was, however, not the case in mice that received the highest dermal amount of TDI (3% on days 1, 2, and 3). These findings suggest that respiratory response to TDI depends on prior frequency and concentration of dermal sensitization in mice.
ISSN: 1096-6080
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Occupational, Environmental and Insurance Medicine (-)
Translational Cell & Tissue Research
Environment and Health - miscellaneous
Laboratory of Clinical Immunology
× corresponding author
# (joint) last author

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