Acute suppressive effect of hydrocortisone on p47phox subunit of nicotinamide adenine dinucleotide phosphate oxidase

Abstract

We have recently demonstrated that reactive oxygen species (ROS) generation by polymorphonuclear leukocytes (PMNL) and mononuclear cells (MNC) is inhibited following the intravenous administration of hydrocortisone. This is associated with a parallel decrease in intranuclear NFκB, known to modulate inflammatory responses including ROS generation. We have also shown that the plasma levels of interleukin-10 (IL-10), an anti-inflammatory and immunosuppressive cytokine produced by TH2 cells, are also increased after hydrocortisone administration. In this study, we have investigated the effect of hydrocortisone on p47phox subunit, a key component of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, in MNC and the pharmacodynamics of this effect with ROS generation and plasma IL-10 levels. p47phox subunit protein levels in MNC showed a progressive decrease after hydrocortisone administration. It reached a nadir at 4 hours and increased thereafter to a baseline level at 24 hours. ROS generation also decreased, reached a nadir between 2 and 4 hours, and returned to a baseline level at 24 hours. IL-10 concentrations increased, peaked at 4 hours, and reverted to the baseline levels at 24 hours. In conclusion, p47phox subunit suppression may contribute to the inhibition of ROS generation in MNC after hydrocortisone administration. This suppression occurs in parallel with the suppression of NFκB and an increase in IL-10 plasma levels. Therefore, it would appear that the decrease in intranuclear NFκB and an increase in IL-10 may cause the inhibitory modulation on p47phox subunit and ROS generation by MNC following hydrocortisone and other glucocorticoids.