title: Respiratory hypersensitivity to trimellitic anhydride in Brown Norway rats: evidence for different activation pattern of immune cells following topical and respiratory induction.
abstract: The elicitation of respiratory allergy in animal models is exquisitely complex and interpretation of results from different laboratories cannot readily be compared due to variability in testing protocols, biomarkers and techniques used to identify 'positive' responses. On the one hand, guinea-pigs have been proposed as a good model with which to study allergic and irritant bronchial hyperresponsiveness. On the other hand, considerable efforts have been made to develop animal models that take the immunological mechanisms into account to reduce the complexity as well as duration of the guinea-pig assays. In principle, local skin reactions can easily be determined by the local lymph node assay (LLNA) introduced by Kimber and Weisenberger. In contrast to lung sensitization there are already simplified and reliable models available to test for and discriminate contact sensitizers from skin irritants, i.e. the modified local lymph node assay IMDS (integrated model for the differentiation of skin reactions). Modifications of this assay verified that methods other than radioactive labelling may be comparably sensitive, and that it is possible to eliminate 'false positive' results induced by irritants (IMDS). Thus, we asked whether there could be a similar simplified model like the modified LLNA or IMDS for investigations of respiratory allergens. Therefore, we analysed immune reactions induced by the dermal and respiratory route, respectively. Analyses of the draining lymph nodes of the lung and the ear were carried out before and after challenge via the pulmonary tract. The results clearly support that (1) the reactions in the lung draining lymph nodes could be used as early indicators of respiratory sensitization, and (2) the specificity of the immune competent cells seem to be dependent of the route of administration during induction.
authors.affiliation: Institute of Toxicology, Bayer AG, 42096 Wuppertal, Germany. hans-werner.vohr.hv@bayer-ag.de
authors.forename: H-W
authors.initials: HW
authors.lastname: Vohr
authors.forename: J
authors.initials: J
authors.lastname: Pauluhn
authors.forename: H J
authors.initials: HJ
authors.lastname: Ahr
mesh_terms: D000280:Administration, Inhalation; D000287:Administration, Topical; D000336:Aerosols; D000485:Allergens / Q000633:toxicity*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D002452:Cell Count; D004431:Ear, External / Q000166:cytology; D005434:Flow Cytometry; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D008297:Male; D010641:Phenotype; D010796:Phthalic Anhydrides / Q000633:toxicity*; D051381:Rats; D011914:Rats, Inbred BN; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000473:pathology; D015656:Respiratory Mechanics / Q000502:physiology
chemical_list: D000336:Aerosols; D000485:Allergens; D010796:Phthalic Anhydrides; C015559:trimellitic anhydride