ToxSci Advance Access originally published online on April 7, 2009
Toxicological Sciences 2009 109(2):265-275; doi:10.1093/toxsci/kfp073
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Patterns of Immunotoxicity Associated with Chronic as Compared with Acute Exposure to Chemical or Physical Stressors and their Relevance with Regard to the Role of Stress and with Regard to Immunotoxicity Testing
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* Department of Cellular Biology & Anatomy, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130
Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi 39762
1 To whom correspondence should be addressed at Department of Basic Sciences, College of Veterinary Medicine, P.O. Box 6100, 240 Wise Center Drive, Mississippi State University, Mississippi State, MS 39762. Fax: (662) 325-8884. E-mail: Pruett{at}cvm.msstate.edu.
Received December 7, 2008; accepted April 3, 2009
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Abstract |
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Previous studies have demonstrated that the stress response induced by some drugs and chemicals contributes in a predictable way to alteration of particular immunological parameters in mice. It has not been determined if mice can become tolerant or habituated with regard to the stress response and consequent immunological effects. Addressing this issue was the purpose of the present study. Mice were dosed daily for 28 days with atrazine, ethanol, propanil, or subjected to restraint, which are known to induce neuroendocrine stress responses and thereby to alter several immunological parameters. On day 29, a blood sample was taken and the spleen was removed for analysis of cellular phenotypes, differential cell counts (for blood), and natural killer (NK) cell activity. Corticosterone concentration at various times after dosing (or restraint) was also measured. Comparison of these results with results from previous studies with a single acute exposure revealed that the corticosterone response was almost completely absent in mice treated with ethanol, reduced in mice treated with restraint and propanil, and for atrazine the response was the same as noted for acute exposure. In most cases, the changes in immunological parameters were consistent with expectations based on these corticosterone responses. However, in a few cases (e.g., NK cell activity), it was clear that there were effects not mediated by stress. These results indicate that the nature of the stressor determines whether mice become tolerant with regard to the stress response and consequent immunological effects. This finding has practical implications for safety testing in mice.
Key Words: stress; corticosterone; immunotoxicology; chronic; acute.
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