Active catabolism of glucocorticoids by 11β-hydroxysteroid dehydrogenase in vivo is a necessary requirement for natural resistance to infection with Listeria monocytogenes

The results from the present study demonstrate that the innate defense mechanisms which control the progressive growth of Listeria monocytogenes in normal animals in vivo are dependent upon the active catabolism of endogenous glucocorticoids by the enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD). When 11β-HSD activity was pharmacologically inhibited in vivo, host susceptibility to progressive bacterial disease was markedly increased. Depressed natural resistance following 11β-HSD inhibition correlated with changes in the patterns of inducible cytokines by macrophages and T cells. Similar changes were observed when normal adult animals were treated with low doses of dexamethasone prior to experimental infection with Listeria.