Modeling and Predicting Immunological Effects of Chemical Stressors: Characterization of a Quantitative Biomarker for Immunological Changes Caused by Atrazine and Ethanol

Abstract

Previous studies demonstrate that the effects of one chemical stressor on selected immunological parameters can be predicted on the basis of the area under the corticosterone concentration vs. time curve. However, it is not clear if this is applicable to other chemical stressors. The present study was conducted to determine if the stress-induced immunological effects of atrazine and ethanol could be predicted, and if it is feasible to use one immunological parameter as a biomarker of stress to predict the quantity of changes expected in other immunological parameters. The area under the corticosterone concentration-versus-time curve (AUC) was measured in mice treated with ethanol (EtOH, 4, 5, 6, or 7 g/kg by oral gavage) or atrazine (ATZ, 100, 200, or 300 mg/kg, ip). The effects of the same dosages of these chemicals on thymus and spleen cellularity, lymphocyte subpopulations in the thymus and spleen, expression of MHC class II protein on splenocytes, antibody responses to keyhole limpet hemocyanin, and natural killer-cell activity were determined. Models were derived describing the relationship between corticosterone AUC and immunological changes induced by these chemicals. The results for these chemical stressors were more similar to results obtained from mice subjected to restraint stress than from mice treated with exogenous corticosterone. Some effects were greater than predicted on the basis of the stress response alone, indicating other mechanisms of immunotoxicity. One of the parameters (MHC class II expression) was evaluated as a predictive biomarker for stress-related immunosuppression, and the results suggest it could be suitable for that purpose.

Evaluation of Acute Immunotoxicity of Aerosolized Aflatoxin B1in Female C57BL/6N Mice

“…High levels of ethanol consumption are known to affect the immune system (Szabo, 1999). Previous studies have reported that an oral dose of ethanol (4 to 7 g/kg) to B 6 C 3 F 1 mice slightly decreased the number of nucleated cells in the spleen but did not effect the percentage of CD4 + and CD8 + cells (Pruett et al, 2003). These results are similar to those observed in this study using ethanol vapor.…”

“…* Significantly different from untreated mice analyzed on the same day at p ≤ 0.05 using students 2-tailed t-test. volume of 20 mL/min, mouse body weight of 0.02 kg, ethanol vapor concentration of 60 mg/L, and 50-100% absorption of the inhaled dose, the maximum ethanol dose to mice in this study was 2.7-5.4 g/kg BW which is within the range used by Pruett et al (2003).…”

Greater Than Additive Suppression of TLR3-Induced IL-6 Responses by Administration of Dieldrin and Atrazine

“…Previous studies have demonstrated that atrazine at all dosages used in this study induce a significant increase in serum corticosterone (Pruett et al, 2003b).…”

“…The concentration of corticosterone used in this experiment is approximately 10% of maximal values that might be expected to be induced by the pesticides or by poly I:C (Pruett et al, 2003b), because ∼90% of corticosterone in mouse serum is bound by corticosterone-binding globulin and not biologically available (Pruett et al, 1999). All treatments slightly but significantly decreased the survival and/or metabolic activity of the cells as indicated by the MTT assay.…”

“…We have reported previously that atrazine induces a vigorous neuroendocrine stress response characterized by increased corticosterone concentrations (Pruett et al, 2003b). To determine if dieldrin has a similar effect, mice were treated with two different dosages, and bled 2 hr later.…”