Acute suppressive effect of hydrocortisone on p47(phox) subunit of nicotinamide adenine dinucleotide phosphate oxidase

We have recently demonstrated that reactive oxygen species (ROS) generation by polymorphonuclear leukocytes (PMNL) and mononuclear cells (MNC) is inhi bited following the intravenous administration of hydrocortisone. This is a ssociated with a parallel decrease in intranuclear NF kappaB, known to modu late inflammatory responses including ROS generation. We have also shown th at the plasma levels of interleukin-10 (IL-10), an anti-inflammatory and im munosuppressive cytokine produced by TH2 cells, are also increased after hy drocortisone administration. In this study, we have investigated the effect of hydrocortisone on p47(phox) subunit, a key component of nicotinamide ad enine dinucleotide phosphate (NADPH) oxidase, in MNC and the pharmacodynami cs of this effect with ROS generation and plasma IL-10 levels. p47(phox) su bunit protein levels in MNC showed a progressive decrease after hydrocortis one administration. It reached a nadir at 4 hours and increased thereafter to a baseline level at 24 hours. ROS generation also decreased, reached a n adir between 2 and 4 hours, and returned to a baseline level at 24 hours. I L-10 concentrations increased, peaked at 4 hours, and reverted to the basel ine levels at 24 hours. In conclusion, p47(phox) subunit suppression may co ntribute to the inhibition of ROS generation in MNC after hydrocortisone ad ministration. This suppression occurs in parallel with the suppression of N F kappaB and an increase in IL-10 plasma levels. Therefore, it would appear that the decrease in intranuclear NF kappaB and an increase in IL-10 may c ause the inhibitory modulation on p47(phox) subunit and ROS generation by M NC following hydrocortisone and other glucocorticoids. Copyright (C) 2001 b y W.B. Saunders Company.