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Markus W. Knöferl, MD; Michael D. Diodato, MD; Martin K. Angele, MD; Alfred Ayala, PhD; William G. Cioffi, MD; Kirby I. Bland, MD; Irshad H. Chaudry, PhD

Arch Surg. 2000;135:425-433.

Hypothesis  Administration of female sex steroids in males after trauma-hemorrhage has salutary effects on the depressed immune responses.

Design  Randomized laboratory experiment.

Interventions  Male C3H/HeN mice were subjected to midline laparotomy and hemorrhagic shock (35 ± 5 mm Hg for 90 minutes, then resuscitation) or sham operation and received subcutaneous 17-estradiol (40 µg/kg body weight) or corn oil vehicle at the beginning of resuscitation.

Main Outcome Measures  At 24 hours after hemorrhage, the animals were killed and plasma 17-estradiol and IL-6, splenocyte interleukin (IL) 2, IL-3, and IL-10 production as well as splenic and peritoneal macrophage IL-1, IL-10, and IL-6 release were measured.

Results  Splenocyte IL-2 and IL-3 release were significantly depressed after hemorrhage in vehicle-treated mice (P<.05, analysis of variance). Treatment with 17-estradiol after hemorrhage led to the restoration of splenocyte IL-2 and IL-3 release. The depressed proinflammatory cytokine (IL-1 and IL-6) release seen in splenic and peritoneal macrophages was restored in the 17-estradiol–treated hemorrhage group. In contrast, the sustained release of the anti-inflammatory cytokine IL-10 by splenocytes and splenic and peritoneal macrophages in vehicle-treated mice after hemorrhage was decreased in 17-estradiol–treated mice. The increase in circulating IL-6 levels after hemorrhage was significantly attenuated in 17-estradiol–treated mice. Although administration of 17-estradiol increased plasma 17-estradiol levels by approximately 100% in sham as well as hemorrhage groups, improved immune responses were seen only in posthemorrhage 17-estradiol–treated mice. There was no adverse effect of 17-estradiol treatment in the sham or posthemorrhage groups.

Conclusion  Since administration of a single dose of 17-estradiol in males after trauma-hemorrhage restores the immune functions and decreases circulating levels of IL-6, hormones with estrogenic properties should be considered as safe and novel therapeutic agents for restoring the immune responsiveness in male trauma victims.

From the Center for Surgical Research and the Department of Surgery, Brown University School of Medicine and Rhode Island Hospital, Providence. Dr Bland is now with the Department of Surgery, University of Alabama at Birmingham School of Medicine.

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