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 specie s (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 though t to be roughly equivalent to 100 mg hydrocortisone. We also tested the hyp othesis that dexamethasone may increase the plasma concentration of interle ukin-10 (IL-10), an immunomodulatory cytokine that inhibits T(H)1 tells. De xamethasone (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 basa l 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 dexamethas one 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 hou rs (F = 66.5; P < .001). The peak inhibitory effect of dexamethasone on mon onuclear cells (11.4% +/- 6.6%) was significantly greater (P <.05) than tha t on polymorphonuclear leukocytes (22.9% +/- 6.4%), Plasma IL-10 concentrat ions increased consistently from 4.8 +/- 1.8 pg/mL within 1 hour of dexamet hasone injection and peaked at 4 hours (8.8 +/- 2.3 pg/mL), declining to ba seline at 8 hours (F = 4.26; P < .004). Dexamethasone (and possibly other g lucocorticoids) therefore exerts its immunosuppressive and anti-inflammator y effects by inhibiting ROS generation by leukocytes and by increasing the plasma concentrations of IL-10.