Toxicological Sciences, Vol 49, 272-280, Copyright © 1999 by Society of Toxicology
SB Pruett, S Collier, WJ Wu and R Fan
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.
ARTICLES
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
Department of Cellular Biology and Anatomy, Louisiana State University Medical Center in Shreveport 71130, USA.
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