11-BETA-HYDROXYSTEROID DEHYDROGENASE MODULATION OF GLUCOCORTICOID ACTIVITIES IN LYMPHOID ORGANS

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.