ToxSci Advance Access published online on August 9, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm194
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Published by Oxford University Press 2007.
Th2 Cytokines in Skin Draining Lymph Nodes and Serum IgE Do Not Predict Airway Hypersensitivity to Intranasal Isocyanate Exposure in Mice
1 Experimental Toxicology Division, U.S. EPA, Research Triangle Park, NC
Corresponding Author E-mail: selgrade.maryjane{at}epa.gov
Received May 9, 2007; revision received July 16, 2007; accepted July 18, 2007
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Abstract |
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Isocyanate exposure in the workplace has been linked to asthma and allergic rhinitis. Recently, investigators have proposed that Th2 cytokine responses in lymph nodes draining the site of dermal application of chemicals including isocyanates may be used to identify sensitizers that cause asthma-like responses. The purpose of this study was to determine if the cytokine profile induced after dermal sensitization with isocyanates and serum IgE predict immediate (IHS) and methacholine-induced late (LHS) respiratory hypersensitivity responses after intranasal challenge. Dermal application of hexylmethane diisocyanate (HMDI), toluene diisocyanate (TDI), or methylene diisocyanate (MDI) significantly increased interleukin-4 (IL-4), IL-5 and IL-13 secretion in parotid lymph node cells. Isophorone diisocyanate (IPDI) increased IL-4 and IL-13, but not IL-5. Tolyl(mono) isocyanate (TMI), tetramethylene xylene diisocyanate (TMXDI) or the contact sensitizer dinitrochlorobenzene (DNCB), only induced minor increases in some of the Th2 cytokines. HMDI, TDI, MDI, and IPDI elicited greater increases in total serum IgE than DNCB, TMI and TMXDI. All chemicals except TMXDI caused IHS after intranasal challenge of sensitized female Balb/c mice. Only HMDI, TMI, or TMXDI sensitized and challenged mice had increases in LHS. All chemicals elicited epithelial cytotoxicity indicative of nasal airway irritation. The discordance between dermal cytokine profiles and respiratory responses suggest that dermal responses do not necessarily predict respiratory responses. Serum IgE also was not predictive of the respiratory responses to the isocyanates suggesting that other unknown mechanisms may be involved.
Disclaimer: This paper has been reviewed and approved for release by the National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency. Approval does not signify that the contents necessarily reflect the views and policies of the U.S. EPA, nor does mention of trade names or commercial products constitute endorsement or recommendation for use.
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