Effect of dexamethasone on reactive oxygen species generation by leukocytes and plasma interleukin-10 concentrations: a pharmacodynamic study.
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 cells. 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.
Dandona
P
P
Division of Endocrinology and Metabolism, State University of New York at Buffalo, and the Kaleida Health System, 14209, USA. pdandona@mfhs.edu
Mohanty
P
P
Hamouda
W
W
Aljada
A
A
Kumbkarni
Y
Y
Garg
R
R
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000097:blood / Q000494:pharmacology*; D003907:Dexamethasone / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D016753:Interleukin-10 / Q000097:blood*; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012016:Reference Values; D014838:Volunteers
D000893:Anti-Inflammatory Agents; D017382:Reactive Oxygen Species; D016753:Interleukin-10; D003907:Dexamethasone