Previous studies have demonstrated that glucocorticoids suppress the immune response to antigen and that restraint stress increases serum corticosterone levels. Additional research using rats has shown that mild, acute restraint stress increases ear swelling and lymphocytic infiltration in allergic contact dermatitis (ACD), but not in irritant contact dermatitis (ICD). We hypothesized that mild restraint stress alters the murine cutaneous response to chemicals and that these changes would be reflected in the cytokine profile and be gender-specific. For ACD studies, male and female B6, 129 mice were sensitized on the flank with 0.5% DNFB (Days 1 & 2) and challenged with 0.25% DNFB on the ear immediately following mild restraint stress (Day 6). For irritant studies, 5% croton oil was applied to the ear immediately after restraint. We measured ear swelling, cytokines TNF-a, IL-lb, IFN-g and IL-4 and serum corticosterone levels as an indicator of activation of the hypothalamic-pituitary axis. Restraint increased serum corticosterone levels in all mice. In the ICD studies, we measured irritant-induced increases in ear thickness and TNF-a and IL-1b production. Ear thickness and TNF-a levels were not altered by restraint stress, however, the concentration of IL-lb was suppressed at 8 and 24 hours. IFN-g and IL-4 were minimally detectable in all treatment conditions. There were no gender differences in the irritant response. For ACD, in both males and females, DNFB induced ear swelling and increased TNF-a, IL-I band IFN-g. Restraint stress coupled with DNFB treatment resulted in an additional, but transient, increase in ear thickness and, at 24 hours, increased IFN-g but decreased IL-lb. TNF-a was more elevated at g and 24 hours in females only, and IL-4 was not detected for any ACD treatment conditions. These data suggest a complex interaction between restraint stress-induced changes in the dermal response to chemicals that may be mediated by elevations in serum glucocorticoids in B6, 129 mice.
The Toxicologist. Society of Toxicology 38th Annual Meeting, March 14-18, 1999, New Orleans, Louisiana