Long-term in vivo administration of glucocorticoid hormones attenuates their capacity to accelerate in vitro proliferation of rat splenic T cells.
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 microg/ml in saline), a physiological replacement dose of CORT (15 microg/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.
Sterzer
Philipp
P
Max Planck Institute of Psychiatry, Munich, Germany.
Wiegers
G Jan
GJ
Reul
Johannes M H M
JM
D000315:Adrenalectomy; D000818:Animals; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology*; D004326:Drinking / Q000187:drug effects; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013154:Spleen / Q000166:cytology*
D007376:Interleukin-2; D011965:Receptors, Glucocorticoid; D015375:Receptors, Interleukin-2; D003345:Corticosterone