Influence of Steroids on Oxidant Generation in Activated Human Granulocytes and Mononuclear Leukocytes
Abstract
ACT Steroids, in particular, 17 -estradiol (E2), have been reported to improve the response to trauma in animal models. In these models, the leukocyte plays a critical role in the inflammatory cascade. We examined the affects of E2 , hydrocortisone (H), progesterone (P ), and E2 with P4 on oxidant production in human granulocytes (PMNs) and mononuclear leukocytes (MNCs). Each cell type was loaded with 2,7-dichlorodihydrofluorescein and then simultaneously activated with human cytokines (tumor necrosis factor , interleukin-1 , and interferon ) and hemoglobin and inhibited with and without equimolar concentrations of each steroid treatment or nitric oxide (NO) synthesis inhibitors. After incubations of 1 or 5 h, intracellular oxidants were quantified by flow cytometry. Activation by cytokines combined with hemoglobin, resulted in a 450 575% increase in oxidant production that was synergistically greater than the sum of either component alone. Pharmacological levels of E2 decreased oxidants in MNCs at 1 h. In contrast at 5 h, H decreased oxidants more than E2 . The addition of P4 to E2 concentrations almost eliminated oxidants from 1 h-activated MNCs. None of the steroids significantly reduced oxidants in PMNs, suggesting that the E2 effect on MNCs was not caused by its nonreceptor-mediated antioxidant properties. Because L-NMMA inhibited at least 55% of the total oxidants, part of E2 dampening effects would be attributed to NO. These results suggest that steroid-attenuated MNC-derived NO may reduce autocrine and paracrine effects on inflammation if appropriate doses of steroids are given soon after injury.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2003
- Accession Number
- ADA628265
Entities
People
- Richard A. Cassidy
Organizations
- United States Army Institute of Surgical Research