TY - JOUR
T1 - Receptor-mediated effects of glucocorticoids on inflammation
T2 - Enhancement of the inflammatory response with a glucocorticoid antagonist
AU - Laue, Louisa
AU - Kawai, Shinichi
AU - Brandon, David D.
AU - Brightwell, David
AU - Barnes, Kevin
AU - Knazek, Richard A.
AU - Loriaux, D. Lynn
AU - Chrousos, George P.
N1 - Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 1988/6
Y1 - 1988/6
N2 - 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 dexamethasome 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 < 0.005). RU 486 was able to antagonize fully the suppressive effects of dexamethasone on the inflammatory response (P < 0.001) and to cause increases of exudate volume and leukocyte, PGE2 and LTB4 concentrations when given alone (P < 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.
AB - 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 dexamethasome 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 < 0.005). RU 486 was able to antagonize fully the suppressive effects of dexamethasone on the inflammatory response (P < 0.001) and to cause increases of exudate volume and leukocyte, PGE2 and LTB4 concentrations when given alone (P < 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.
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U2 - 10.1016/0022-4731(88)90156-2
DO - 10.1016/0022-4731(88)90156-2
M3 - Article
C2 - 2838686
AN - SCOPUS:0023944251
SN - 0022-4731
VL - 29
SP - 591
EP - 598
JO - Journal of Steroid Biochemistry
JF - Journal of Steroid Biochemistry
IS - 6
ER -