Identification of contact and respiratory sensitizers according to IL-4 receptor α expression and IL-2 production

• Published in: Toxicology and applied pharmacology Vol. 260; no. 2; pp. 95 - 104
• Main Authors: Goutet, Michèle, Pépin, Elsa, Langonné, Isabelle, Huguet, Nelly, Ban, Masarin
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 15.04.2012; Elsevier
• Subjects: 60 APPLIED LIFE SCIENCES; Allergens - classification; Allergens - immunology; ANHYDRIDES; Animals; ASTHMA; Biological and medical sciences; Chemical contact and respiratory sensitizers; Dinitrochlorobenzene - immunology; Female; Flow Cytometry; Hypersensitivity - immunology; IgE-positive B cells; IL-2; IL-4; IL-4Rα; Immunoglobulin E - blood; Immunoglobulin E - immunology; Interleukin-2 - biosynthesis; Interleukin-2 - immunology; Local Lymph Node Assay; Medical sciences; MICE; Mice, Inbred BALB C; MOLECULES; OCCUPATIONAL SAFETY; Phthalic Anhydrides - immunology; RECEPTORS; Receptors, Cell Surface - biosynthesis; Receptors, Cell Surface - immunology; SENSITIZERS; Statistics, Nonparametric; TOLUENE; Toxicology; IL-4; Flow cytometry; IL-2; IgE-positive B cells; Chemical contact and respiratory sensitizers; IL-4Rα; Chemical compound; IgE; Cytokine; Biosynthesis; Identification; B-Lymphocyte; Respiratory system; Interleukin 4; Interleukin 2; Chemosensitizing agent; Sensitizer; Biological receptor
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2012.02.009

Identification of allergenic chemicals is an important occupational safety issue. While several methods exist to identify contact sensitizers, there is currently no validated model to predict the potential of chemicals to act as respiratory sensitizers. Previously, we reported that cytometry analysis of the local immune responses induced in mice dermally exposed to the respiratory sensitizer trimellitic anhydride (TMA 10%) and contact sensitizer dinitrochlorobenzene (DNCB 1%) could identify divergent expression of several immune parameters. The present study confirms, first, that IgE-positive B cells, MHC class II molecules, interleukin (IL)-2, IL-4 and IL-4Rα can differentiate the allergic reactions caused by high doses of strong respiratory (TMA, phthalic anhydride and toluene diisocyanate) and contact sensitizers (DNCB, dinitrofluorobenzene and oxazolone). The second part of the study was designed to test the robustness of these markers when classing the weakly immunogenic chemicals most often encountered. Six respiratory allergens, including TMA (2.5%), five contact allergens, including DNCB (0.25%), and two irritants were compared at doses of equivalent immunogenicity. The results indicated that IL-4Rα and IL-2 can be reliably used to discriminate sensitizers. Respiratory sensitizers induced markedly higher IL-4Rα levels than contact allergens, while irritants had no effect on this parameter. Inversely, contact allergens tended to induce higher percentages of IL-2+CD8+ cells than respiratory allergens. In contrast, the markers MHC-II, IgE and IL-4 were not able to classify chemicals with low immunogenic potential. In conclusion, IL-4Rα and IL-2 have the potential to be used in classifying a variety of chemical allergens. ► Identification of chemical allergens is an important occupational safety issue. ► There is currently no model to predict the potential of chemicals to induce asthma. ► We analyze immune responses induced in mice by a variety of chemical sensitizers. ► IL-2 and IL-4R alpha show potential to discriminate between both types of allergens. ► This method could be applied to highly and weakly immunogenic chemicals.