11̄-Hydroxysteroid dehydrogenase modulation of glucocorticoid activities in lymphoid organs

The immunoregulatory effects of glucocorticoids (GCS) are linked to their capacity to alter the production of various species of cytokines associated with immune and inflammatory processes. The present study determined that the influences of GCS within particular lymphoid organs vary, depending on the specific activity of 11β-hydroxysteroid dehydrogenase (11β-HSD) within the tissue. This enzyme converts active GCS to inactive metabolites and was found to display greater activity in peripheral than in mucosal lymphoid organs. A direct correlation was found between 11β-HSD activity and the preferential production of type 1 cytokines by T-cells residing within certain lymphoid organs. It was established that lymphoid organ 11β-HSD was localized in the immobile stromal cell components. Inhibition of 11β-HSD activity in vivo reduced type i and enhanced type 2 cytokine production by activated T-cells, and it also depressed the ability of animals to generate contact hypersensitivity responses. We conclude that GCS levels can be controlled within lymphoid organs through oxidative inactivation by 11β-HSD. GCS action is, therefore, dependent on tissue levels of 11β-HSD activity, the number of GCS receptors in a responsive cell, and the concentration of circulating GCS.