An increase in basal glucocorticoid concentration with age induces suppressor macrophages with high‐density FcγRII/III

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Abstract
Ageing is usually accompanied by a decline in immune and neuroendocrine functions. To elucidate the mechanisms underlying age‐related immunosuppression, the functions and surface phenotypes of peritoneal cells in the monocyte/macrophage lineage from old mice were investigated. The role of glucocorticoids (GC) in the immunomodulation was also examined. Proliferative responses of spleen cells from control mice stimulated with concanavalin A (Con A) were significantly suppressed by adding peritoneal exudate cells from old mice. Flow cytometry analysis revealed that the proportion of MAC‐1+ cells with a high density of type II or type III receptor for the Fc portion of IgG (FcγRII/IIIbright cells) was increased markedly in the peritoneal exudate cells from old mice. The prominent suppressor activity for Con A responses of control spleen cells was found in the FcγRII/IIIbright cells, whereas MAC‐1+ cells with a low density of FcγRII/III (FcγRII/IIIdull cells) did not suppress the Con A responses. On the other hand, both the basal corticosterone concentrations in serum and the mRNA expression for GC receptor in peritoneal exudate cells increased significantly in old mice. Furthermore, the proportion of FcγRII/IIIbright cells in peritoneal exudate cells from old mice was normalized on administration of the GC antagonist RU 38 486 (mifepristone). These results suggest that the increase in basal corticosterone concentrations in old mice induces the generation of FcγRII/IIIbright suppressor cells, possibly leading to the immune‐suppressive state.