Social stress induces glucocorticoid resistance in macrophages

Stress-induced levels of plasma glucocorticoid hormones are known to modula te leukocyte function. These experiments examined the effects of a social s tressor on the responsiveness of peripheral immune cells. Male mice experie nced six evening cycles of social disruption (SDR), in which an aggressive male intruder was placed into their home cage for 2 h. Although circulating corticosterone was elevated in SDR mice, they had enlarged spleens and inc reased numbers of splenic leukocytes. Splenocytes from SDR and control mice were cultured with lipopolysaccharide and corticosterone. Cells from SDR m ice exhibited decreased sensitivity to the antiproliferative effects of cor ticosterone, suggesting that the peripheral immune cells were resistant to glucocorticoids. In addition, SDR cells produced more interleukin (IL)-6. T o determine which cell population was affected, we used antibody-labeled ma gnetic beads to deplete splenocyte suspensions of B cells or macrophages. D epletion of macrophages from SDR cultures, but not depletion of B cells, ab olished both the corticosterone resistance and enhanced IL-6 secretion. The se findings demonstrate that a psychosocial stressor induced glucocorticoid resistance in mouse splenic macrophages.