Active catabolism of glucocorticoids by 11 beta-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 defensemechanisms which control the progressive growth of Listeria monocytogenesin normal animals in vivo are dependent upon the active catabolism ofendogenous glucocorticoids by the enzyme 11 beta- hydroxysteroiddehydrogenase (11 beta-HSD). When 11 beta-HSD activity waspharmacologically inhibited in vivo, host susceptibility to progressivebacterial disease was markedly increased. Depressed natural resistancefollowing 11 beta-HSD inhibition correlated with changes in the patterns ofinducible cytokines by macrophages and T cells. Similar changes wereobserved when normal adult animals were treated with low doses ofdexamethasone prior to experimental infection with Listeria.