Jd. Hennebold et al., 11-BETA-HYDROXYSTEROID DEHYDROGENASE MODULATION OF GLUCOCORTICOID ACTIVITIES IN LYMPHOID ORGANS, American journal of physiology. Regulatory, integrative and comparative physiology, 39(6), 1996, pp. 1296-1306
The immunoregulatory effects of glucocorticoids (GCS) are linked to th
eir capacity to alter the production of various species of cytokines a
ssociated with immune and inflammatory processes. The present study de
termined that the influences of GCS within particular lymphoid organs
vary, depending on the specific activity of 11 beta-hydroxysteroid deh
ydrogenase (11 beta-HSD) within the tissue. This enzyme converts activ
e GCS to inactive metabolites and was found to display greater activit
y in peripheral than in mucosal lymphoid organs. A direct correlation
was found between 11 beta-HSD activity and the preferential production
of type 1 cytokines by T-cells residing within certain lymphoid organ
s. It was established that lymphoid organ 11 beta-HSD was localized in
the immobile stromal cell components. Inhibition of 11 beta-HSD activ
ity in vivo reduced type 1 and enhanced type 2 cytokine production by
activated T-cells, and it also depressed the ability of animals to gen
erate contact hypersensitivity responses. We conclude that GCS levels
can be controlled within lymphoid organs through oxidative inactivatio
n by 11 beta-HSD. GCS action is, therefore, dependent on tissue levels
of 11 beta-HSD activity, the number of GCS receptors in a responsive
cell, and the concentration of circulating GCS.