Laue L, Kawai S, Brandon D D, Brightwell D, Barnes K, Knazek R A, Loriaux D L, Chrousos G P
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892.
J Steroid Biochem. 1988 Jun;29(6):591-8. doi: 10.1016/0022-4731(88)90156-2.
Glucocorticoids suppress the inflammatory response by altering leukocyte traffic and function, cytokine secretion and action, and phospholipid metabolism. We employed the glucocorticoid receptor antagonist RU 486, to examine whether glucocorticoids suppress the inflammatory response through a receptor-mediated mechanism and whether basal glucocorticoid secretion exerts antiinflammatory effects in the resting (non-stress) state. To test these hypotheses we evaluated the effects of increasing doses of dexamethasone, RU 486, or dexamethasone plus RU 486 on the exudate volume and concentrations of leukocytes, prostaglandin E2, (PGE2) and leukotriene B4 (LTB4) in intact rats that received subcutaneous carrageenin. Exudate volume, leukocyte concentration and LTB4 and PGE2 levels were all suppressed by dexamethasone in a dose-dependent fashion (P less than 0.005). RU 486 was able to antagonize fully the suppressive effects of dexamethasone on the inflammatory response (P less than 0.001) and to cause increases of exudate volume and leukocyte, PGE2 and LTB4 concentrations when given alone (P less than 0.05). These increases ranged between 30 and 100% above the basal inflammatory response. We conclude that glucocorticoids most likely suppress the inflammatory response by a glucocorticoid receptor-mediated mechanism and under basal conditions exert tonic antiinflammatory effects.
糖皮质激素通过改变白细胞运输与功能、细胞因子分泌与作用以及磷脂代谢来抑制炎症反应。我们使用糖皮质激素受体拮抗剂RU 486，以研究糖皮质激素是否通过受体介导机制抑制炎症反应，以及基础糖皮质激素分泌在静息（非应激）状态下是否发挥抗炎作用。为验证这些假设，我们评估了递增剂量的地塞米松、RU 486或地塞米松加RU 486对皮下注射角叉菜胶的完整大鼠渗出液体积以及白细胞、前列腺素E2（PGE2）和白三烯B4（LTB4）浓度的影响。地塞米松以剂量依赖方式抑制渗出液体积、白细胞浓度以及LTB4和PGE2水平（P<0.005）。RU 486能够完全拮抗地塞米松对炎症反应的抑制作用（P<0.001），并且单独给药时会导致渗出液体积以及白细胞、PGE2和LTB4浓度增加（P<0.05）。这些增加幅度比基础炎症反应高出30%至100%。我们得出结论，糖皮质激素很可能通过糖皮质激素受体介导机制抑制炎症反应，并且在基础条件下发挥持续性抗炎作用。
