11 beta-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 t...

Full description

Saved in:
Bibliographic Details
Published inThe American journal of physiology Vol. 270; no. 6 Pt 2; p. R1296
Main Authors Hennebold, J D, Ryu, S Y, Mu, H H, Galbraith, A, Daynes, R A
Format Journal Article
LanguageEnglish
Published United States 01.06.1996
Subjects
11-beta-Hydroxysteroid Dehydrogenases
Animals
Cytokines - biosynthesis
Female
Glucocorticoids - metabolism
Hydroxysteroid Dehydrogenases - physiology
Isoenzymes - metabolism
Liver - enzymology
Lymphocyte Activation
Lymphoid Tissue - enzymology
Mice
Mice, Inbred C3H
Stromal Cells - enzymology
T-Lymphocytes - metabolism
T-Lymphocytes - physiology
Online AccessGet more information

Cover

More Information
Summary: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 11 beta-hydroxysteroid dehydrogenase (11 beta-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 11 beta-HSD activity and the preferential production of type 1 cytokines by T-cells residing within certain lymphoid organs. It was established that lymphoid organ 11 beta-HSD was localized in the immobile stromal cell components. Inhibition of 11 beta-HSD activity in vivo reduced type 1 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 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.
ISSN:0002-9513
DOI:10.1152/ajpregu.1996.270.6.R1296