Plasma corticosterone and immune reactivity in restrained female C3H mice

Psychological stressors are known to stimulate the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system resulting in the release of corticosterone and catecholamines respectively. They have also been reported to induce cytokine production. All these molecules affect various immune parameters and can alter overall immune competence of the individual. The purpose of this investigation was to study the regulation of the production of corticosterone during stress and its possible effects on immune reactivity. In a first series of experiments, the possible regulation of corticosterone production by interleukin (IL)-1beta and peripheral catecholamines during restraint was assessed using a pharmacological approach in mice. Plasma IL-1beta concentrations remained at basal after 1-h restraint and the stress-induced increase of plasma corticosterone was not modified by a peripheral injection of an IL-1 receptor antagonist (IL-1ra). By contrast, chemical sympathectomy potentiated the restraint-induced increase in plasma corticosterone concentration, this potentiation being reversed by IL-1ra. In a second series of experiments, the role of corticosterone in stress-immune relationships was studied in adrenalectomized mice subjected to restraint and immunized with sheep erythrocytes. Non-specific immunity, i.e. proliferation of splenocytes and thymocytes and plasma levels of IL-1beta, as well as specific immunity, i.e. antibody production and delayed hypersensitivity, were not altered after 2-h restraint. Adrenalectomy failed to induce immune effects in stressed animals, except that delayed hypersensitivity was stronger in adrenalectomized animals, revealing that the high levels of corticosterone produced during stress have an anti-inflammatory activity. The present data show that the stress-induced production of corticosterone was modulated by both peripheral catecholamines and IL-1beta. However, this production of corticosterone was unable to modulate immune reactivity except delayed hypersensitivity.