This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sterzer, P. Articles by Reul, J. M. H. M. Search for Related Content PubMed PubMed Citation Articles by Sterzer, P. Articles by Reul, J. M. H. M.

Long-Term in Vivo Administration of Glucocorticoid Hormones Attenuates Their Capacity to Accelerate in Vitro Proliferation of Rat Splenic T Cells

Max Planck Institute of Psychiatry (P.S., G.J.W., J.M.H.M.R.), Section of Neuropsychopharmacology, 80804 Munich, Germany; Department of Neurology (P.S.), Johann Wolfgang Goethe-University, D-60590 Frankfurt am Main, Germany; Institute of Pathophysiology (G.J.W.), University of Innsbruck, Medical School, A-6020 Innsbruck, Austria; and Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology (J.M.H.M.R.), University of Bristol, Bristol BS1 3NY, United Kingdom

Address all correspondence and requests for reprints to: Dr. Johannes M. H. M. Reul, Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, The Dorothy Hodgkin Building, University of Bristol, Whitson Street, Bristol BS1 3NY, United Kingdom. E-mail: hans.reul{at}bristol.ac.uk.

Previous work has shown that glucocorticoids accelerate splenic T cell proliferation in vitro. To test whether chronic exposure to high levels of glucocorticoids in vivo would affect this accelerating effect, we offered adrenalectomized rats a high dose of corticosterone (CORT; 150 µg/ml in saline), a physiological replacement dose of CORT (15 µg/ml in saline), or saline to drink. We also included a group of sham-adrenalectomized rats. After 1 wk of treatment, splenic lymphocytes of these animals were cultured in the presence or the absence of 1000 nM CORT. The central finding was that the CORT-evoked acceleration of the proliferative response in vitro was attenuated in splenic T cells from animals that had received the high-dose CORT treatment in vivo. This observation could not be explained by changes in IL-2 levels in culture supernatants, the cellular composition of the spleens, or an altered glucocorticoid receptor expression in T cells. As a candidate mechanism, we identified the abrogation of a CORT-evoked enhancement of IL-2 receptor expression. This finding underscores the pivotal role of the IL-2 receptor in the modulation of cellular immunity by glucocorticoids. We conclude that the attenuated acceleration of T cell proliferation after long-term exposure to elevated glucocorticoid levels may underlie the well-known impairment of immune function under chronic stress.