Diurnal and Acute Stress-Induced Changes in Distribution of Peripheral Blood Leukocyte Subpopulations
ABSTRACT In this study, we examined hormonal regulation of the distribution profiles of leukocyte subpopulations in the peripheral blood of rats. Flow cytometric analysis revealed significant and selective changes in the numbers and the percentages of peripheral blood leukocyte subpopulations which were a function of diurnal variations in hormone secretion and hormonal changes induced by acute stress. Changes in numbers and percentages of leukocyte subpopulations, which varied with time of day, were similar to changes observed under stress conditions. At the beginning of the rat's active period, and after 1 h of restraint stress, there was a significant reduction in numbers of leukocytes and lymphocytes. This reduction was primarily accounted for by a decrease in numbers of B cells, natural killer cells, monocytes (diurnal study), and helper T cells (diurnal study). There was also a significant decrease in the percentage of lymphocytes which was mirrored by an increase in the percentage of neutrophils in the peripheral blood. Peripheral blood leukocyte numbers were inversely related to plasma corticosterone levels. These results suggest that the endocrine system plays a role in the regulation of immune cell turnover and/or redistribution between immune compartments under conditions of normal daily experiences, namely, the diurnal cycle, and mild acute stress. They also suggest that these effects are selective for certain subpopulations of leukocytes.
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ABSTRACT: Different stressors likely elicit different physiological and behavioral responses. Previously reported differences in the effects of stressors on immune function may reflect qualitatively different physiological responses to stressors; alternatively, both large and subtle differences in testing protocols and methods among laboratories may make direct comparisons among studies difficult. Here we examine the effects of chronic stressors on plasma corticosterone concentrations, leukocyte redistribution, and skin delayed-type hypersensitivity (DTH), and the effects of acute stressors on plasma corticosterone and leukocyte redistribution. The effects of several commonly used laboratory stressors including restraint, forced swim, isolation, and low ambient temperatures (4 degrees C) were examined. Exposure to each stressor elevated corticosterone concentrations, with restraint (a putative psychological stressor) evoking a significantly higher glucocorticoid response than other stressors. Chronic restraint and forced swim enhanced the DTH response compared to the handled, low temperature, or isolation conditions. Restraint, low temperature, and isolation significantly increased trafficking of lymphocytes and monocytes compared to forced swim or handling. Generally, acute restraint, low temperature, isolation, and handling increased trafficking of lymphocytes and monocytes. Considered together, our results suggest that the different stressors commonly used in psychoneuroimmunology research may not activate the physiological stress response to the same extent. The variation observed in the measured immune responses may reflect differential glucocorticoid activation, differential metabolic adjustments, or both processes in response to specific stressors.Brain Behavior and Immunity 02/2008; 22(1):105-13. DOI:10.1016/j.bbi.2007.07.012 · 6.13 Impact Factor
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ABSTRACT: Eleven mammalian toll-like receptors (TLRs 1-11) have been identified to date and are known to play a crucial role in the regulation of immune responses; however, the factors that regulate TLR expression and function in vivo are poorly understood. Therefore, in the present study, we investigated the physiological regulation of TLR expression and function in humans. To examine the influence of diurnal rhythmicity on TLR expression and function, peripheral venous blood samples were collected from healthy volunteers (n = 8) at time points coinciding with the peak and nadir in the endogenous circulating cortisol concentration. While no diurnal rhythmicity in the expression of TLRs 1, 2, 4 or 9 was observed, the upregulation of costimulatory (CD80 and CD86) and antigen-presenting (MHC class II) molecules on CD14(+) monocytes following activation with specific TLR ligands was greater (P < 0.05) in samples obtained in the evening compared with the morning. To examine the influence of physical stress on TLR expression and function, peripheral venous blood samples were collected from healthy volunteers (n = 11) at rest and following 1.5 h of strenuous exercise in the heat (34 degrees C). Strenuous exercise resulted in a decrease (P < 0.005) in the expression of TLRs 1, 2 and 4 on CD14(+) monocytes. Furthermore, the upregulation of CD80, CD86, MHC class II and interleukin-6 by CD14(+) monocytes following activation with specific TLR ligands was decreased (P < 0.05) in samples obtained following exercise compared with at rest. These results demonstrate that TLR function is subject to modulation under physiological conditions in vivo and provide evidence for the role of immunomodulatory hormones in the regulation of TLR function.The Journal of Physiology 04/2005; 563(Pt 3):945-55. DOI:10.1113/jphysiol.2004.081224 · 4.54 Impact Factor
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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.Toxicological Sciences 02/2005; 83(1):101-13. DOI:10.1093/toxsci/kfi014 · 4.48 Impact Factor