11b-hydroxysteroid dehydrogenase modulation of glucocorticoid
activities in lymphoid organs.
Hennebold[acute]a, Jon D., Si-Yun Ryu[acute]a, Hong-Hua Mu[acute]a,
Anne Galbraith[acute]a, Raymond A. Daynes[acute]a.
Department of Pathology, University of Utah School of Medicine,
Salt Lake City, Utah 84132, Geriatric Research, Education and
Clinical Center, Veterans Affairs Medical Center, Salt Lake City,
Utah 84112
APStracts 3:0024R, 1996.
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 upon the specific activity of 11b
-hydroxysteroid dehydrogenase (11b-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 11b-HSD activity and the
preferential production of Type 1 cytokines by T cells residing
within certain lymphoid organs. It was established that lymphoid
organ 11b-HSD was localized to the immobile, stromal cell components.
Inhibition of 11b-HSD activity in vivo reduced Type 1 and enhanced
Type 2 cytokine production by activated T cells, and 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 11b-HSD. GCS action
is, therefore, dependent on tissue levels of 11b-HSD activity, the
number of GCS receptors in a responsive cell, and the concentration
of circulating GCS.
Received 3 October 1995; accepted in final form 8 January 1996.
APS Manuscript Number R620-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 January 96