EFFECTS OF VIRAL-INFECTION ON CORTICOSTERONE SECRETION AND GLUCOCORTICOID RECEPTOR-BINDING IN IMMUNE TISSUES

During an immune challenge it has been suggested (hat responding cells secrete cytokines which then stimulate the release of glucocorticoids . Glucocorticoids, in turn, are believed to bind to their receptors in target immune tissues and provide feedback inhibition on evolving imm une responses. The foundations for this hypothesis have been drawn pri marily from studies on animal models of autoimmune and/or inflammatory processes, and the relevance of these glucocorticoid-immune interacti ons to viral infections has not been extensively examined. Accordingly , we infected mice with lymphocytic choriomeningitis virus (LCMV) and measured plasma corticosterone and cytosolic glucocorticoid receptor ( GR) binding at multiple time points throughout the day and throughout infection (days 3, 5, 7 and 10 post infection). Despite a vigorous imm une response to this virus, LCMV infection was associated with minimal and transient increases in corticosterone secretion. Interestingly, h owever, significant decreases in cytosolic GR were found in immune tis sues. Receptor decreases were characterized by a significant decrease in GR binding during the diurnal rise in corticosterone in the spleen and thymus of infected but not uninfected animals on days 5-10 post in fection. In addition, in the morning on these days, GR binding in the spleen of infected mice was decreased compared to uninfected control m ice. Following an acute injection of corticosterone on day 7 post infe ction, LCMV-infected animals exhibited a significantly greater decreas e in splenic GR binding than uninfected control mice, suggesting an in creased sensitivity to corticosterone in infected animals. No changes were found in the affinity (K-d) Of the GR during infection, nor was t here evidence of an infection-associated decrease in plasma corticoste roid binding globulin. The appearance of significant GR changes in the spleen and thymus, in the absence of significant elevations in cortic osterone or decreases in its binding protein, suggests that cytokines and/or other. factors produced within the immune tissues during infect ion either directly influenced GR number and/or function or influenced the local availability of corticosterone. Taken together, the results indicate that interactions between the neuroendocrine and immune syst ems can be modified at the level of the GR in the context of an ongoin g immune response such as during a viral infection. (C) 1997 Elsevier Science Ltd.