Effect of dexamethasone on reactive oxygen species generation by leukocytes and plasma interleukin-10 concentrations: A pharmacodynamic study

被引:53
作者
Dandona, P
Mohanty, P
Hamouda, W
Aljada, A
Kumbkarni, Y
Garg, R
机构
[1] SUNY Buffalo, Div Endocrinol & Metab, Diabet Endocrinol Ctr Western New York, Buffalo, NY 14209 USA
[2] Kaleida Hlth Syst, Buffalo, NY USA
关键词
D O I
10.1016/S0009-9236(99)70054-8
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
After the demonstration that hydrocortisone inhibits reactive oxygen species (ROS) generation by leukocytes in vivo in a highly predictable manner, we investigated the effect of dexamethasone at a dose of 4 mg,which is thought to be roughly equivalent to 100 mg hydrocortisone. We also tested the hypothesis that dexamethasone may increase the plasma concentration of interleukin-10 (IL-10), an immunomodulatory cytokine that inhibits T(H)1 tells. Dexamethasone (4 mg given intravenously) markedly inhibited ROS generation by mononuclear cells and polymorphonuclear leukocytes,The onset of the effect on polymorphonuclear leukocytes occurred at 1 hour (76.3% +/- 9.3% of basal value), and the peak effect occurred at 4 hours (22.9% +/- 6.4% of basal value), with a significant inhibition still persistent at 8 hours (51.3% +/- 14.3% of basal value; F = 66.7; P < .001), ROS generation was restored to baseline at 24 hours (97.6% +/- 9.5%). The inhibitory effect of dexamethasone on mononuclear cells was 78.3% +/- 9.5% of baseline at 1 hour, 11.4% +/- 6.6% at 4 hours, 30.3% +/- 14.1% at 8 hours, and 102.3% +/- 18% at 24 hours (F = 66.5; P < .001). The peak inhibitory effect of dexamethasone on mononuclear cells (11.4% +/- 6.6%) was significantly greater (P <.05) than that on polymorphonuclear leukocytes (22.9% +/- 6.4%), Plasma IL-10 concentrations increased consistently from 4.8 +/- 1.8 pg/mL within 1 hour of dexamethasone injection and peaked at 4 hours (8.8 +/- 2.3 pg/mL), declining to baseline at 8 hours (F = 4.26; P < .004). Dexamethasone (and possibly other glucocorticoids) therefore exerts its immunosuppressive and anti-inflammatory effects by inhibiting ROS generation by leukocytes and by increasing the plasma concentrations of IL-10.
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页码:58 / 65
页数:8
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