Effects of 17β-estradiol and flutamide on inflammatory response and distant organ damage following trauma-hemorrhage in metestrus females

Journal of Leukocyte Biology

Bjoern M. Thobe¹  Mashkoor A. Choudhry¹  Frank Hildebrand¹  Irshad H. Chaudry¹  Hans-Christoph Pape²  William J. Hubbard¹ 

[1] Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham Alabama; and Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham Alabama; and Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham Alabama; and;Department of Orthopedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania Department of Orthopedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania Department of Orthopedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania

关键词: cytokines;    liver;    lungs;    neutrophil infiltration;    edema;   

DOI  :  10.1189/jlb.0406254

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

We hypothesized that administration of androgen receptors antagonist flutamide following trauma-hemorrhage (T-H) in metestrus females will maintain immune function and reduce remote organ damage under those conditions. Female B57BL/J6 mice (metestrus state, 8–12 weeks old) underwent laparotomy and hemorrhagic shock (35.0±5.0 mmHg for 90 min) and then received 17β-estradiol (E2; 50 μg/25 g), flutamide (625 μg/25 g), or E2 + flutamide. Four hours after resuscitation, plasma cytokine and chemokine (TNF-α, IL-6, IL-10, IFN-γ, and MCP-1) concentrations and their release in vitro by hepatic and pulmonary tissue macrophages (MΦ) were determined by flow cytometry. Organ damage was assessed by edema formation (wet-to-dry weight ratio) and neutrophil infiltration [myeloperoxidase (MPO) activity]. Administration of E2, flutamide, or E2 + flutamide following T-H resulted in a significant decrease in systemic TNF-α, IL-6, and MCP-1 concentrations under those conditions. This was accompanied by significantly decreased in vitro TNF-α release by Kupffer cells after administration of E2, flutamide, or E2 + flutamide. The in vitro release of proinflammatory cytokines by alveolar MΦ, however, was reduced significantly only by the addition of E2 or E2 + flutamide but not by the addition of flutamide. A significant decrease in pulmonary and hepatic edema formation as well as neutrophil infiltration in the lung was observed after E2, flutamide and E2 + flutamide administration. In contrast, hepatic neutrophil infiltration was only significantly reduced following E2 and E2 + flutamide administration. Thus, although flutamide does not produce synergistic, salutary effects with E2, its administration in females following T-H also produces salutary effects on the immune and organ function, similar to E2 administration under those conditions.

【 授权许可】

Unknown