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The neuroendocrine response to stressors increases the concentration of several endogenous mediators, some of which are immunosuppressive. However, quantitative aspects of these effects have been overlooked. Although it should be possible to predict the degree of suppression of particular immunological functions by measuring the concentrations of stress-related mediators such as corticosterone, this cannot be done with data presently available. This study was designed to develop regression models to predict the relationship between the area under the corticosterone concentration vs. time curve (AUC) and two immunological parameters. Models were developed using mice treated with exogenous corticosterone and mice subjected to various periods of restraint stress. The latter treatment was included to determine if the effects of corticosterone were different from those of corticosterone in association with the other mediators induced in a restraint-stress response. Models relating corticosterone AUC to expression of MHC class II proteins on splenocytes were very similar, whether the corticosterone was exogenous or produced as part of a restraint-stress response. This was also true for splenic natural killer (NK) cell activity. However, MHC class II expression was more sensitive to the effects of corticosterone or restraint than was NK cell activity. The corticosterone and restraint models predicted the previously published effect of a chemical stressor (ethanol) on MHC class II expression, but neither model predicted the suppression of NK cell activity by ethanol. These results have mechanistic implications, which are discussed in the context of previous studies. The quantitative models described here should be useful in determining and predicting the stress-related portion of chemical-induced immunosuppression. In addition, these models provide quantitative data essential for a complete understanding of stress-induced immunosuppression.

toxicological sciences

Quantitative relationships between the suppression of selected immunological parameters and the area under the corticosterone concentration vs. time curve in B6C3F1 mice subjected to exogenous corticosterone or to restraint stress