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The contact allergen dinitrochlorobenzene (DNCB) and respiratory allergy in the Th2-prone Brown Norway rat

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Author: Kuper, C.F. · Stierum, R.H. · Boorsma, A. · Schijf, M.A. · Prinsen, M. · Bruijntjes, J.P. · Bloksma, N. · Arts, J.H.E.
Institution: TNO Kwaliteit van Leven
Source:Toxicology, 2-3, 246, 213-221
Identifier: 240761
doi: doi:10.1016/j.tox.2008.01.013
Keywords: Health · Dinitrochlorobenzene · LLNA · MCP-1 · MIP1-beta · Respiratory allergy · Skin allergy · 1 chloro 2,4 dinitrobenzene · CD4 antigen · immunoglobulin G · macrophage inflammatory protein 1beta · monocyte chemotactic protein 1 · monocyte chemotactic protein 3 · thymus and activation regulated chemokine · animal experiment · animal model · animal tissue · article · controlled study · female · lung function · lung lavage · lung parenchyma · male · microarray analysis · nonhuman · Norway · nucleotide sequence · priority journal · rat · respiratory tract allergy · skin allergy · skin irritation · skin sensitization · Th2 cell · upregulation · Administration, Cutaneous · Allergens · Animals · Dermatitis, Allergic Contact · Dinitrochlorobenzene · Female · Immunoglobulin E · Immunoglobulin G · Inhalation Exposure · Irritants · Local Lymph Node Assay · Lung · Lymph Nodes · Male · Rats · Rats, Inbred BN · Rats, Wistar · Respiratory Function Tests · Respiratory Hypersensitivity · Th2 Cells · Animalia · Rattus · Rattus norvegicus


All LMW respiratory allergens known to date can also induce skin allergy in test animals. The question here was if in turn skin allergens can induce allergy in the respiratory tract. Respiratory allergy was tested in Th2-prone Brown Norway (BN) rats by dermal sensitization with the contact allergen dinitrochlorobenzene (DNCB; 1%, day 0; 0.5%, day 7) and a head/nose-only inhalation challenge of 27 mg/m3 of DNCB (15 min, day 21), using a protocol that successfully identified chemical respiratory allergens. Skin allergy to DNCB was examined in BN rats and Th1-prone Wistar rats in a local lymph node assay followed by a topical patch challenge of 0.1% DNCB. Sensitization of BN rats via the skin induced DNCB-specific IgG in serum, but not in all animals, and an increased number of CD4+ cells in the lung parenchyma. Subsequent inhalation challenge with DNCB did not provoke apneas or allergic inflammation (signs of respiratory allergy) in the BN rats. However, microarray analysis of mRNA isolated from the lung revealed upregulation of the genes for Ccl2 (MCP-1), Ccl4 (MIP-1beta), Ccl7 and Ccl17. Skin challenge induced considerably less skin irritation and allergic dermatitis in the BN rat than in the Wistar rat. In conclusion, the Th2-prone BN rat appeared less sensitive to DNCB than the Wistar rat; nevertheless, DNCB induced allergic inflammation in the skin of BN rats but even a relatively high challenge concentration did not induce allergy in the respiratory tract, although genes associated with allergy were upregulated in lung tissue. © 2008 Elsevier Ireland Ltd. All rights reserved.