RATIONALE: Epidemiology studies have identified the quaternary ammonium compound (QAC) didecyldimethlyammonium chloride (DDAC) as a workplace asthmagen, yet our studies have indicated that DDAC is a T-cell mediated dermal sensitizer. As health care workers are exposed to a variety of chemicals concurrently, we hypothesized that previous exposure to an IgE-mediated sensitizer, (Ortho-phthalaldehyde [OPA]) may alter immune responses to DDAC. METHODS: BALB/C mice were exposed to OPA (0.5%) on the dorsal ear surface for 3-days, rested, then exposed to DDAC (0.0625, 0.125, 0.25%) for 14-days. Vehicle, OPA-only, and DDAC-only (0.25%) controls were included for all studies. Body weight and ear thickness were monitored, and 1-day following final exposure markers of allergic disease were assessed by RT-PCR and flow cytometry in the draining lymph-node (dLN); total IgE (serum) was measured by ELISA. RESULTS: Animals sensitized to OPA prior to DDAC exposure (0.25%) exhibited increased irritation and weight loss (;-5% v. ;0%) compared to DDAC-only controls. The co-exposed mice also had enhanced Th2 responses, including significant (p < 0.05) alterations in: dLN Il4 (increased, all doses), B-cell activation (increased, all doses), CD8 T-cell activation (decreased, all doses), and increases in local (0.0625% and 0.125%), and systemic IgE production (0.125% and 0.25%). CONCLUSIONS: Animals exposed to an IgE mediated sensitizer (OPA), prior to a T-cell sensitizer (DDAC) showed enhanced Th2/IgE immune responses, highlighting the potential for mixed exposures to impact allergic disease. As IgE is linked to respiratory sensitizers, this data may partially explain the discordance between epidemiological and laboratory studies in regards to QACs.

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