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 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 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD). When 11 beta-HSD activity was pharmacologically inhibited in vivo, host susceptibility to progressive bacterial disease was markedly increased. Depressed natural resistance following 11 beta-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.
Hennebold
J D
JD
Department of Pathology, University of Utah School of Medicine, Salt Lake City 84132, USA.
Mu
H H
HH
Poynter
M E
ME
Chen
X P
XP
Daynes
R A
RA
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D004198:Disease Susceptibility; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism*; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000502:physiology*; D007113:Immunity, Innate / Q000187:drug effects; D008088:Listeriosis / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL
D016207:Cytokines; D005938:Glucocorticoids; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases