Development of a combined irritancy/phenotypic analysis assay for the identification and differentiation of chemicals with the potential to elicit irritation, IgE-mediated, or T cell mediated hypersensitivity responses.
Allergic and irritant dermatitis account for 15-20% of reported occupational diseases, resulting in an estimated annual loss of one billion dollars due to decreased productivity (NIOSH, 1996). There remains a need to develop rapid, reproducible, cost effective methods to screen chemicals for their ability to induce these responses. To this end several murine models have been developed. The irritancy assay, local lymph node assay, and serum total IgE-ELISA represent three models proposed to identify chemical irritants, chemical sensitizers and IgE-medicated hypersensitivity-inducing chemicals, respectively (Kimber et al., 1994; Potter et al., 1995; Woolhiser et al., 1998). Using flow cytometric analysis, Katona et al., (1983) observed an increased level of IgE+ draining mesenteric lymph node cells in mice undergoing an IgE response to parasitic infection with Nippostrongylus brasiliensis. Previous studies in this lab (data not shown) and others (Sikorski et al., 1996; Gerberick et al., 1997) have shown an elevation in the percent of B220+draining lymph node cells following dermal exposure to T-cell medicated hypersensitivity-inducing allergens. Using three end points: the percent increase in ear swelling, the percent increase in IgE+B220+draining lymph node cells, and the percent increase in B220+draining lymph node cells, these studies investigate the potential use of a single combined murine irritancy/phenotypic analysis assay to identify and differentiate chemicals with the capacity to elicit irritation, IgE-mediated, or T-cell medicated hypersensitivity responses.
B. Jean Meade, National Institute for Occupational Safety and Health, 1095 Willowdale Rd MS 4020, Morgantown, WV 26505