Acute stress modulates the irritant component of sensitizers in allergic contact dermatitis: implications for exposure assessment

Abstract

Exposure of skin to noxious environmental stimuli can cause allergic contact dermatitis (ACD), which is a major health risk. Epidemiological studies have determined that 40% of workers report that their jobs are very, or extremely, stressful, and the number of chemicals to which workers are exposed increases each year. We hypothesized that combined exposure to a workplace stressor and a sensitizing chemical would alter the time course and magnitude of the skin immune response. We assessed the mixed exposure of chemical and restraint stress using three potent skin sensitizers, 2,4 dinitrofluorbenzene (DNFB), dicyclohexylcarbodiimide (DCC), and oxazolone, (OXA) on the ear swelling response in stress-susceptible BALB/c mice. Quantitative analyses showed that the dose-response relationship for each chemical followed a cubic trend. Although stress did not alter the shape of the curve, application of restraint stress on day 1 or on day 6 diminished the ear swelling response to 0.1% DNFB. However, if the concentration of the challenge dose was increased to a more irritating concentration, 0.25% DNFB, ear swelling was enhanced. Restraint stress applied on day 6 also increased ear swelling in response to the highly irritating sensitizer DCC, but not to the low-irritancy chemical OXA. These data support the hypothesis that dose-response relationships exist for sensitization with chemical and that restraint stress modulation of the ear swelling response is both chemical specific and dependent on the irritancy potential of the chemical.