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ToxSci Advance Access published online on October 27, 2004

Toxicological Sciences, doi:10.1093/toxsci/kfi014
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
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Received August 11, 2004
Accepted October 19, 2004

Immunotoxiocology

Modeling and Predicting Stress-Induced Immunosuppression in Mice Using Blood Parameters

Carlton L. Schwab 1, Ruping Fan 1, Qiang Zheng 1, L. Peyton Myers 1, Pamela Hébert 1, and Stephen B. Pruett 1*

1 Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport, LA

* To whom correspondence should be addressed.
Stephen B. Pruett, E-mail: spruet{at}lsuhsc.edu


   Abstract

Previous studies have shown that the area under the corticosterone concentration vs. time curve (AUC) can be used to model and predict the effects of restraint stress and chemical stressors on a variety of immunological parameters in the mouse spleen and thymus. In order to complete a risk assessment parallelogram, similar data are needed with blood as the source of immune system cells, because this is the only tissue routinely available from human subjects. Therefore, studies were conducted using treatments for which the corticosterone AUC values are already known: exogenous corticosterone, restraint, propanil, atrazine, and ethanol. Immunological parameters were measured using peripheral blood from mice treated with a series of dosages of each of these agents. Flow cytometry was used to quantify MHC II, B220, CD4, and CD8 cells. Leukocyte and differential counts were done. Spleen cell number and NK cell activity were evaluated to confirm similarity to previous studies. Immune parameter data from mouse blood indicate that MHC II expression has consistent quantitative relationships to corticosterone AUC values, similar to but less consistent than those observed in the spleen. Other immune parameters tended to have greater variability in the blood than in the spleen. The pattern observed in the spleen in which the chemical stressors generally produced very similar effects as noted for restraint stress (at the same corticosterone AUC values) was not observed for blood leukocytes. Nevertheless, MHC class II expression seems to provide a reasonably consistent indication of stress exposure in blood and spleen.

Keywords: Modeling; stress; biomarker; ethanol; atrazine; propanil.
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