You are here:
CYTOKINE PROFILES DO NOT PREDICT ANTIBODY RESPONSES AND RESPIRATORY HYPERRESPONSIVENESS FOLLOWING DERMAL EXPOSURE TO ISOCYANATES
Citation:
SELGRADE, M. K., E. BOYKIN, N. HAYKAL-COATES, M. R. WOOLHISER, C. WIESCINSKI, D. L. ANDREWS, A. FARRAJ, D. L. DOERFLER, AND S. H. GAVETT. CYTOKINE PROFILES DO NOT PREDICT ANTIBODY RESPONSES AND RESPIRATORY HYPERRESPONSIVENESS FOLLOWING DERMAL EXPOSURE TO ISOCYANATES. Presented at American Academy of Allergy, Asthma and Immunology Annual Meeting 2007, San Diego, CA, February 23 - 27, 2007.
Description:
Rationale: Cytokine profiling of local lymph node responses following dermal exposure has been proposed as a test to identify chemicals that pose a risk of occupational asthma. The present study tested the hypothesis that relative differences in cytokine profiles for dinitrochlorobenzene (DNCB) and six isocyanates: toluene diisocyanate (TDI), diphenylmethane-4,4¿-diisocyanate (MDI), dicyclohexylmethane-4,4¿diisocyanate (HMDI), isophorone diisocyanate (IPDI), p-tolyl(mono)isocyanate (TMI), and meta-tetramethylene xylene diisocyanate (TMXDI) are predictive of relative differences in total serum IgE and respiratory responses to methacholine (Mch) following dermal exposure to the chemicals. Methods: BALB/c mice received 9 dermal exposures over a period of 28 days to one of the chemicals, or vehicle. Mice were then challenged with increasing doses of Mch and respiratory responsiveness was assessed using whole body plethysmography. Serum antibody responses and cytokine mRNA profiles in the draining lymph node were also assessed. In separate experiments, cytokine protein assays were performed after 5 dermal exposures over a 14 day period. Results: The response pattern for IL-4, IL-10, and IL-13 for the different isocyanates was highly reproducible as determined by RNAse protection, RT-PCR or cytokine protein levels. However, the relative differences in these responses were not predictive of relative differences in total serum IgE or Mch responsiveness.
Conclusions: The data suggest that cytokine profiling needs to be further developed and that other approaches to hazard identification should be pursued. The weight of evidence from all the assays performed suggests that all 6 isocyanates tested have some potential to cause respiratory hypersensitivity following dermal exposure. (This abstract does not reflect EPA policy).