Stressor-specific alterations in corticosterone and immune responses in mice

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.

Figure 1

Timeline for Experiment 1.

Figure 2

Delayed-type hypersensitivity (DTH) responses after 4 wks of stressor treatments. All increases are significantly different from zero. Restraint and forced swim elicited significantly higher DTH responses post-challenge than the low temperature, isolation, or handled stressors. *as compared to low temperature, isolation, and handle; # as compared to isolation and handle; ^ as compared to swim (p<0.05 for all)

Figure 3

Baseline (day 0), pre-, and post-stress (day 15) corticosterone concentrations. Restraint elicited higher corticosterone values than all other stressor treatments. Only restraint, forced swim, and low temperature induced significantly elevated corticosterone concentrations following stressor treatment compared to their respective day 15 baseline. *Significant difference between pre- and post-stress; “A” is higher than all other groups, “B” higher than “C.”

Figure 4

Blood leukocyte populations on day 25(chronic) or after one stressor treatment (acute). Chronic -Restraint, low temperature, and isolation significantly increased trafficking of lymphocytes and monocytes to a greater extent than forced swim or handling. Restraint induced a larger increase in circulating neutrophils than isolation. Acute - Restraint resulted in higher stress-induced changes in lymphocytes than low temperature, forced swim, and handling; in addition, isolation induced larger changes than forced swim. Monocytes trafficked significantly more out of the blood in the restraint, low temperature, and isolation groups than in the forced swim group. Restraint and isolation also resulted in significantly different changes in neutrophil populations than forced swim. Significance is specific to each panel (cell type and stressor duration): * significant difference between pre- and post-stress levels within treatment; “A” is significantly different from “B” which is different from “C”.

Figure 5

Corticosterone concentrations after one (acute) session of treatment. All stressor treatments significantly elevated corticosterone concentrations compared to baseline. “A” is significantly different from “B”.