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CYTOKINE RESPONSES TO DERMAL ISOCYANATE EXPOSURE IN DRAINING LYMPH NODES ARE NOT PREDICTIVE OF AIRWAY RESPONSES AFTER AIRWAY CHALLENGE
Citation:
FARRAJ, A., E. BOYKIN, N. HAYKAL-COATES, S. H. GAVETT, AND M. K. SELGRADE. CYTOKINE RESPONSES TO DERMAL ISOCYANATE EXPOSURE IN DRAINING LYMPH NODES ARE NOT PREDICTIVE OF AIRWAY RESPONSES AFTER AIRWAY CHALLENGE. Presented at 45th Annual Society of Toxicology Meeting 2006, San Diego, CA, March 05 - 09, 2006.
Description:
Exposure to low molecular weight chemicals including isocyanates has been linked to occupational asthma. A strong need exists for the rapid and accurate identification of chemical respiratory sensitizers. Recently, some investigators have proposed that chemicals may be identified as respiratory sensitizers if they elicit a Th2 cytokine response in lymph nodes draining the site of dermal application in mice, without examining respiratory responses. The main purpose of this study was to determine if the cytokine profile induced after dermal sensitization with isocyanates in draining lymph nodes predicts the respiratory hypersensitivity responses after intranasal challenge. Dermal application of toluene diisocyanate (TDI), methylene diisocyanate (MDI), or hexylmethane diisocyanate (HMDI) resulted in an increase in the secretion of the Th2 cytokines interleukin(IL)-4 and IL-5 from excised draining lymph node cells. Dermal application of isophorone diisocyanate (IPDI) resulted in an increase in IL-4, but not IL-5. Dermal application of tolyl(mono) isocyanate (TMI), tetramethylene xylene diisocyanate (TMXDI) or the contact sensitizer dinitrochlorobenzene (DNCB), an inducer of Th1 cytokines, did not induce increases in any of the Th2 cytokines. Both DNCB and TDI induced an increase in the Th1 cytokine interferon-γ. DNCB and all the isocyanates except TMXDI caused an increase in immediate airway hypersensitivity after dermal sensitization and intranasal challenge compared to corresponding non-sensitized mice. Only TMI or HMDI sensitized and challenged mice, however, had increases in methacholine-induced airflow obstruction. While the cytokine response is predictive of the airway response to HMDI, TMXDI or DNCB, it is not predictive of the airway response to MDI, TMI, IPDI, or TDI. The data suggest that cytokine responses at the site of dermal exposure to a chemical respiratory sensitizer may not be predictive of the airway response after airway challenge (This abstract does not reflect EPA policy).