Restraint stress is associated with changes in glucocorticoid immunoregulation

Abstract

Psychological stress has been associated with activation of the hypothalamic–pituitary–adrenal (HPA) axis and impaired cell-mediated immune (CMI) responses. There is also evidence suggesting that intermittent chronic stress differentially alters CMI across different immune compartments, but the mechanisms underlying this phenomenon have not been explored in detail. In the present study, we investigated (i) acute and chronic restraint stress effects in Sprague–Dawley rats on both peripheral blood lymphocyte (PBL) and splenocyte mitogen-induced proliferation and (ii) also determined whether differential stress effects within these immune compartments might reflect alterations in lymphocyte sensitivity to glucocorticoids. It was found that while acute stress exposure significantly raised plasma corticosterone levels (1048% vs. controls, P<.001), this response was attenuated in the animals previously exposed to chronic intermittent stress (−79.66% vs. acute; P<.001). Acute stress increased phytohemagglutinin (PHA)-induced lymphocyte proliferation in the spleen (69.04%, P=.01) and suppressed PBL proliferation (−45.52%, P<.001). Neither of these changes were observed following chronic stress. We also demonstrated that reexposure to the stressor rapidly increased splenocyte sensitivity to in vitro dexamethasone ( P<.05) and corticosterone ( P<.05) in chronically stressed rats. Our data (1) confirm that acute stress is associated with compartment-specific changes in CMI function, (2) indicate that chronic stress is associated with habituated endocrine and immune responses and (3) that stressor exposure rapidly alters splenocyte sensitivity to glucocorticoids and we suggest that the latter may contribute to differential stress effects across immune compartments.