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Methods for the identification of chemical respiratory allergens in rodents: comparisons of cytokine profiling with induced changes in serum IgE
Author(s) -
Dearman R. J.,
Skinner R. A.,
Humphreys N. E.,
Kimber I.
Publication year - 2003
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.907
Subject(s) - trimellitic anhydride , immunoglobulin e , toluene diisocyanate , local lymph node assay , sensitization , immunology , respiratory system , allergy , cytokine , chemistry , respiratory tract , allergen , antibody , medicine , skin sensitization , organic chemistry , polymer chemistry , polyurethane
No validated or widely recognized test methods are currently available for the prospective identication of chemicals with the potential to cause respiratory allergy. The cellular and molecular mechanisms that result in the induction of chemical sensitization of the respiratory tract are unclear, although there is evidence for the selective development of T helper 2 (Th2)‐type responses and, in some cases, the production of IgE antibody. We have therefore examined the utility of cytokine proling using BALB/c mice, together with the measurement of induced increases in the total serum concentration of IgE in the Brown Norway (BN) rat, as markers for the prospective identication of chemical respiratory allergens. Responses provoked by the reference respiratory allergen trimellitic anhydride (TMA) have been compared with those stimulated by the respiratory sensitizing diisocyanates toluene diisocyanate (TDI) and hexamethylene diisocyanate (HDI) and by the acid anhydride hexahydrophthalic anhydride (HHPA). Topical exposure of BN rats to TMA, TDI and HHPA each provoked marked immune activation (increases in lymph node cellularity and proliferation). However, only treatment with TMA stimulated vigorous increases in the total serum concentration of IgE. In contrast, exposure to HHPA, TDI or HDI failed to provoke signicant changes in serum IgE concentration or induced only transient and relatively weak increases in serum IgE levels. In parallel experiments using BALB/c strain mice, however, topical application of all four chemical respiratory allergens provoked a marked Th2‐type cytokine secretion prole in draining lymph node cells. These data suggest that the measurement of induced changes in serum IgE is not sufciently sensitive for the robust identication of chemical respiratory allergens. Furthermore, irrespective of the reasons for variations in TMA‐induced IgE production among BN rats, doubts remain regarding the utility of these animals for the characterization of immune responses to chemical allergens. Cytokine proling using the BALB/c strain mouse apparently provides a more robust method for the hazard assessment of chemical respiratory allergens. Copyright © 2003 John Wiley & Sons, Ltd.