OBJECTIVE: The contribution of gender to the mortality and morbidity of trauma patients is controversial. In addition, a genetic contribution has been recently indicated. The influence of these two variables was studied in a murine model of endotoxemia. DESIGN: Prospective, controlled, and randomized animal study. SETTING: A university research laboratory. SUBJECTS: Female and male mice (6-8 wks old) were injected with lipopolysaccharide (15 mg/kg). Additionally, mice were gonadectomized and supplemented with 5-alpha-dihydrotestosterone (357 mg/day), 17-beta-estradiol (23.8 microg/day), or placebo for 21 days and injected with lipopolysaccharide. Tumor necrosis factor-alpha was measured in plasma samples obtained after 1.5 hrs of lipopolysaccharide injection. MEASUREMENTS AND MAIN RESULTS: Higher tumor necrosis factor-alpha plasma levels were observed in C57BL/6J (B6) female mice as compared with males. Because this phenotype is not sex linked, we evaluated the role of sex steroids. Castrated male B6 mice showed higher lipopolysaccharide-induced tumor necrosis factor-alpha plasma levels than nonoperated controls. These lipopolysaccharide-induced tumor necrosis factor-alpha levels were further increased after the administration of 17-beta-estradiol to castrated B6 male mice as compared with nonoperated male or female mice. In addition, 17-beta-estradiol-supplemented castrated mice showed a higher frequency of mortality than castrated males without hormone replacement or nonoperated mice. Analysis of castrated male mice from other strains (A/J, DBA/2J, AKR/J, BALB/cJ) supplemented with 17-beta-estradiol presented the opposite effect, a reduction in lipopolysaccharide-induced tumor necrosis factor-alpha plasma levels. CONCLUSIONS: These results suggest that sex steroids can modulate the inflammatory response and the outcome after injury in mice. The effect of sex steroids depends on the genetic background.
OBJECTIVE: The contribution of gender to the mortality and morbidity of traumapatients is controversial. In addition, a genetic contribution has been recently indicated. The influence of these two variables was studied in a murine model of endotoxemia. DESIGN: Prospective, controlled, and randomized animal study. SETTING: A university research laboratory. SUBJECTS: Female and male mice (6-8 wks old) were injected with lipopolysaccharide (15 mg/kg). Additionally, mice were gonadectomized and supplemented with 5-alpha-dihydrotestosterone (357 mg/day), 17-beta-estradiol (23.8 microg/day), or placebo for 21 days and injected with lipopolysaccharide. Tumor necrosis factor-alpha was measured in plasma samples obtained after 1.5 hrs of lipopolysaccharide injection. MEASUREMENTS AND MAIN RESULTS: Higher tumor necrosis factor-alpha plasma levels were observed in C57BL/6J (B6) female mice as compared with males. Because this phenotype is not sex linked, we evaluated the role of sex steroids. Castrated male B6 mice showed higher lipopolysaccharide-induced tumor necrosis factor-alpha plasma levels than nonoperated controls. These lipopolysaccharide-induced tumor necrosis factor-alpha levels were further increased after the administration of 17-beta-estradiol to castrated B6 male mice as compared with nonoperated male or female mice. In addition, 17-beta-estradiol-supplemented castrated mice showed a higher frequency of mortality than castrated males without hormone replacement or nonoperated mice. Analysis of castrated male mice from other strains (A/J, DBA/2J, AKR/J, BALB/cJ) supplemented with 17-beta-estradiol presented the opposite effect, a reduction in lipopolysaccharide-induced tumor necrosis factor-alpha plasma levels. CONCLUSIONS: These results suggest that sex steroids can modulate the inflammatory response and the outcome after injury in mice. The effect of sex steroids depends on the genetic background.
Authors: Robert Drummond; Donghuan Song; Dennis Hawisher; Paul L Wolf; Daniel E Vazquez; Diego F Nino; Raul Coimbra; David M Cauvi; Antonio De Maio Journal: J Surg Res Date: 2011-01-22 Impact factor: 2.192
Authors: Rachna Chandra; Stephanie Federici; Zoltán H Németh; Balázs Csóka; James A Thomas; Robert Donnelly; Zoltán Spolarics Journal: J Leukoc Biol Date: 2013-11-05 Impact factor: 4.962
Authors: Greg Tsang; Michael B Insel; Justin M Weis; Mary Anne M Morgan; Michael S Gough; Lauren M Frasier; Cynthia M Mack; Kathleen P Doolin; Brian T Graves; Michael J Apostolakos; Anthony P Pietropaoli Journal: Crit Care Date: 2016-10-21 Impact factor: 9.097
Authors: Kiichiro Yano; Yoshiaki Okada; Guido Beldi; Shou-Ching Shih; Natalya Bodyak; Hitomi Okada; Peter M Kang; William Luscinskas; Simon C Robson; Peter Carmeliet; S Ananth Karumanchi; William C Aird Journal: J Exp Med Date: 2008-10-13 Impact factor: 14.307