Hydrocortisone-induced inhibition of reactive oxygen species by polymorphonuclear neutrophils

Objective: To determine whether hydrocortisone given intravenously inhibits reactive oxygen species (ROS) generation by poly-morphonuclear neutrophils (PMNLs) in vivo and, if so, to describe the pharmacodynamics of this effec t. Design: A prospective, open label study in normal subjects. Setting: A clinical research unit of a tertiary referral center for diabete s and endocrinology. Patients: Eight normal subjects (age range, 24-50 yrs). Intervention: An indwelling cannula was inserted into the antecubital vein, Sequential blood samples were obtained from the cannula just before, and a fter, the intravenous injection of hydrocortisone (100 mg) at 1, 2, 4, 8, a nd 24 hrs. Measurements and Main Results: ROS generation by PMNLs and mononuclear cell s (MNCs) was assayed as previously observed in a chemiluminometer, ROS gene ration by PMNLs and MNCs was inhibited by hydrocortisone at 1 hr; this effe ct peaked at 2 hrs and began to recover by 4 hrs; ROS generation had recove red to the baseline by 24 hrs, Although the pharmacodynamic effect of hydro cortisone on PMNLs and MNCs was similar, the peak inhibition was significan tly greater for PMNLs (26% of basal vs, 43% of basal, p < .02) than MNCs. Conclusions: There is a marked, consistent, inhibition of ROS generation by PMNLs, which parallels that of MNCs after intravenous hydrocortisone, The pharmacodynamics of this effect are consistent with our current clinical pr actices.