Stress- and aging-associated modulation of macrophage functions

Effects of environmental (cold) stress and aging on cells in monocyte/macrophage lineage were investigated. We demonstrated that immune suppressive states seen in acute cold-stressed mice (8–10 weeks of age) is attributable to FcγRII bright suppressor macrophages. Serum corticosterone levels were markedly increased in acute cold-stressed mice. In addition, expression of glucocorticoids (GC) receptor mRNA was observed in FcγRII bright cells from these mice. The increase of FcγRII bright cells in peritoneal exudate cells caused by acute cold stress was inhibited by adrenalectomy or administration of a saturating amount of the GC antagonist RU 38486 (mifepristone). On the contrary, administration of the GC agonist, dexamethasone, markedly increased the proportion of FcγRII bright cells in peritoneal exudate cells of control mice. These results suggest that the generation of FcγRII bright suppressor cells of monocyte/macrophage lineage by acute cold stress was mediated by action of GC through the GC receptor. We likewise found that the proportion of FcγRII bright suppressor macrophages is increased in aged mice (22–24 months of age). Meanwhile, activated macrophages which function as antigen presenting cells were decreased in aged rats. Both the basal corticosterone concentrations in serum and the expression of mRNA for GC receptor in peritoneal macrophages increased significantly in aged animals, suggesting that these populational and functional changes of macrophages in aged animals were mediated, in part, by the increased basal levels of GC. This is probably being responsible for immunosenescence.