Glucocorticoids enhance concanavalin A-induced mitogenic response through the inhibition of nitric oxide production.
Glucocorticoids (GC) are known to inhibit mitogen-induced proliferation of T cells. In this study we show two experimental situations where the addition of GC increases lymphocyte proliferation. It has been reported by different authors that rat spleen (SPL) cells proliferate poorly after concanavalin A (Con A) activation. These poor responses have been related to the suppressor activity of macrophages. Similarly, it is known that T-cell proliferation is depressed in the presence of an excess of macrophages in the culture. Here we show that in both experimental situations, the inclusion of dexamethasone (DEX), a synthetic glucocorticoid, in the culture medium enhances the Con A-stimulated proliferation. We provide evidence that this effect is a consequence of the inhibition of nitric oxide (NO) synthesis by the hormone. Furthermore, we also demonstrate that rat SPL cells are inefficient antigen-presenting cells (APC) because of their spontaneous high production of NO. Taken together our results suggest that the effects of GC on T-cell activation may be to promote or inhibit proliferation depending on the level of endogenous NO synthesis. The possible significance of these results is briefly discussed.
Ramírez
F
F
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Silva
A
A
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D003208:Concanavalin A / Q000276:immunology*; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000276:immunology; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D013154:Spleen / Q000166:cytology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D005938:Glucocorticoids; D007376:Interleukin-2; D003208:Concanavalin A; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D003907:Dexamethasone