Quantitative analysis of the neuroendocrine-immune axis: Linear modeling of the effects of exogenous corticosterone and restraint stress on lymphocyte subpopulations in the spleen and thymus in female B6C3F1 mice

The effects of exogenous corticosterone and restraint stress on the number and percentage of lymphocyte subpopulations in the spleen and thymus were e valuated. The data were used to generate linear models that describe the re lationship between these parameters and the area under the corticosterone c oncentration vs time curve (AUC). Comparison of the models revealed that th e number of nucleated cells in the spleen was decreased similarly by exogen ous corticosterone and restraint (at equivalent corticosterone AUC values). However, exogenous corticosterone caused a greater decrease in cell number in the thymus than it did in the spleen. Corticosterone preferentially dep leted CD4(+)CD8(+) cells in the thymus, whereas the same corticosterone exp osure produced by restraint stress did not. In the spleen, cell number for all major cell types was decreased by both treatments, but there were minor differences in the change in percentage of some subpopulations induced by exogenous corticosterone as compared to restraint. The models derived here provide quantitative data that indicate the magnitude of corticosterone and stress-induced effects on lymphocyte populations in the spleen and thymus. These results have mechanistic implications, and they may be useful in fut ure efforts to extrapolate from mouse to human by completing a risk assessm ent parallelogram. (C) 2000 Academic Press.