Female sex hormones regulate macrophage function after trauma-hemorrhage and prevent increased death rate from subsequent sepsis

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

Research output: Contribution to journalArticle

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Abstract

Objective: To determine whether reduction of circulating female sex hormones by ovariectomy causes suppression of macrophage (Mφ) function after trauma-hemorrhage and increases susceptibility to subsequent sepsis. Summary Background Data: Studies indicate that immune functions are markedly depressed in males but not in proestrus females after trauma-hemorrhage. Although male sex steroids are immunosuppressive, it remains unknown whether female sex hormones are immunoprotective after trauma-hemorrhage. Methods: Circulating female sex hormones were reduced by ovariectomy of 8-week-old female CBA/J mice. Two weeks afterward, ovariectomy and proestrus sham-ovariectomy mice were subjected to laparotomy (i.e., soft tissue trauma) and hemorrhagic shock (35 ± 5 mm Hg for 90 minutes, then resuscitated) or sham operation. Two hours afterward, splenic and peritoneal Mφ and Kupffer cells were isolated and cytokine production was assessed. In a second series of experiments, animals were subjected to sepsis by cecal ligation and puncture at 24 hours after trauma-hemorrhage or sham operation, and survival was assessed. Results: Release of interleukin-1 and interleukin-6 by splenic and peritoneal Mφ from proestrus mice was maintained after trauma-hemorrhage, whereas release of interleukin-1 and interleukin-6 by Mφ from ovariectomized mice was depressed by approximately 50%. In contrast, trauma-hemorrhage resulted in a fourfold increase of Kupffer cell release of tumor necrosis factor-alpha in ovariectomized females and a fivefold increase in plasma concentrations of tumor necrosis factor-alpha. Release of tumor necrosis factor-alpha and plasma concentrations were unchanged in proestrus mice under such conditions. When proestrus and ovariectomized animals were subjected to sepsis by cecal ligation and puncture at 24 hours after trauma-hemorrhage or sham operation, ovariectomized mice had a significantly higher death rate than proestrus mice. Conclusions: These findings suggest that female sex hormones play a critical role in maintaining immune responses after trauma-hemorrhage by suppressing the elaboration of tumor necrosis factor-alpha and prevent the increased lethality from subsequent sepsis. Thus, female sex hormones may be a useful adjunct in preventing trauma-induced immunodepression and increased susceptibility to subsequent sepsis.

Original languageEnglish (US)
Pages (from-to)105-112
Number of pages8
JournalAnnals of Surgery
Volume235
Issue number1
DOIs
StatePublished - 2002
Externally publishedYes

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Gonadal Steroid Hormones
Sepsis
Proestrus
Macrophages
Hemorrhage
Mortality
Wounds and Injuries
Ovariectomy
Tumor Necrosis Factor-alpha
Kupffer Cells
Interleukin-1
Punctures
Ligation
Interleukin-6
Inbred CBA Mouse
Hemorrhagic Shock
Immunosuppressive Agents
Laparotomy
Immunosuppression
Steroids

ASJC Scopus subject areas

  • Surgery

Cite this

Female sex hormones regulate macrophage function after trauma-hemorrhage and prevent increased death rate from subsequent sepsis. / Knöferl, Markus W.; Angele, Martin K.; Diodato, Michael D.; Schwacha, Martin G; Ayala, Alfred; Cioffi, William G.; Bland, Kirby I.; Chaudry, Irshad H.

In: Annals of Surgery, Vol. 235, No. 1, 2002, p. 105-112.

Research output: Contribution to journalArticle

Knöferl, Markus W. ; Angele, Martin K. ; Diodato, Michael D. ; Schwacha, Martin G ; Ayala, Alfred ; Cioffi, William G. ; Bland, Kirby I. ; Chaudry, Irshad H. / Female sex hormones regulate macrophage function after trauma-hemorrhage and prevent increased death rate from subsequent sepsis. In: Annals of Surgery. 2002 ; Vol. 235, No. 1. pp. 105-112.
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abstract = "Objective: To determine whether reduction of circulating female sex hormones by ovariectomy causes suppression of macrophage (Mφ) function after trauma-hemorrhage and increases susceptibility to subsequent sepsis. Summary Background Data: Studies indicate that immune functions are markedly depressed in males but not in proestrus females after trauma-hemorrhage. Although male sex steroids are immunosuppressive, it remains unknown whether female sex hormones are immunoprotective after trauma-hemorrhage. Methods: Circulating female sex hormones were reduced by ovariectomy of 8-week-old female CBA/J mice. Two weeks afterward, ovariectomy and proestrus sham-ovariectomy mice were subjected to laparotomy (i.e., soft tissue trauma) and hemorrhagic shock (35 ± 5 mm Hg for 90 minutes, then resuscitated) or sham operation. Two hours afterward, splenic and peritoneal Mφ and Kupffer cells were isolated and cytokine production was assessed. In a second series of experiments, animals were subjected to sepsis by cecal ligation and puncture at 24 hours after trauma-hemorrhage or sham operation, and survival was assessed. Results: Release of interleukin-1 and interleukin-6 by splenic and peritoneal Mφ from proestrus mice was maintained after trauma-hemorrhage, whereas release of interleukin-1 and interleukin-6 by Mφ from ovariectomized mice was depressed by approximately 50{\%}. In contrast, trauma-hemorrhage resulted in a fourfold increase of Kupffer cell release of tumor necrosis factor-alpha in ovariectomized females and a fivefold increase in plasma concentrations of tumor necrosis factor-alpha. Release of tumor necrosis factor-alpha and plasma concentrations were unchanged in proestrus mice under such conditions. When proestrus and ovariectomized animals were subjected to sepsis by cecal ligation and puncture at 24 hours after trauma-hemorrhage or sham operation, ovariectomized mice had a significantly higher death rate than proestrus mice. Conclusions: These findings suggest that female sex hormones play a critical role in maintaining immune responses after trauma-hemorrhage by suppressing the elaboration of tumor necrosis factor-alpha and prevent the increased lethality from subsequent sepsis. Thus, female sex hormones may be a useful adjunct in preventing trauma-induced immunodepression and increased susceptibility to subsequent sepsis.",
author = "Kn{\"o}ferl, {Markus W.} and Angele, {Martin K.} and Diodato, {Michael D.} and Schwacha, {Martin G} and Alfred Ayala and Cioffi, {William G.} and Bland, {Kirby I.} and Chaudry, {Irshad H.}",
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T1 - Female sex hormones regulate macrophage function after trauma-hemorrhage and prevent increased death rate from subsequent sepsis

AU - Knöferl, Markus W.

AU - Angele, Martin K.

AU - Diodato, Michael D.

AU - Schwacha, Martin G

AU - Ayala, Alfred

AU - Cioffi, William G.

AU - Bland, Kirby I.

AU - Chaudry, Irshad H.

PY - 2002

Y1 - 2002

N2 - Objective: To determine whether reduction of circulating female sex hormones by ovariectomy causes suppression of macrophage (Mφ) function after trauma-hemorrhage and increases susceptibility to subsequent sepsis. Summary Background Data: Studies indicate that immune functions are markedly depressed in males but not in proestrus females after trauma-hemorrhage. Although male sex steroids are immunosuppressive, it remains unknown whether female sex hormones are immunoprotective after trauma-hemorrhage. Methods: Circulating female sex hormones were reduced by ovariectomy of 8-week-old female CBA/J mice. Two weeks afterward, ovariectomy and proestrus sham-ovariectomy mice were subjected to laparotomy (i.e., soft tissue trauma) and hemorrhagic shock (35 ± 5 mm Hg for 90 minutes, then resuscitated) or sham operation. Two hours afterward, splenic and peritoneal Mφ and Kupffer cells were isolated and cytokine production was assessed. In a second series of experiments, animals were subjected to sepsis by cecal ligation and puncture at 24 hours after trauma-hemorrhage or sham operation, and survival was assessed. Results: Release of interleukin-1 and interleukin-6 by splenic and peritoneal Mφ from proestrus mice was maintained after trauma-hemorrhage, whereas release of interleukin-1 and interleukin-6 by Mφ from ovariectomized mice was depressed by approximately 50%. In contrast, trauma-hemorrhage resulted in a fourfold increase of Kupffer cell release of tumor necrosis factor-alpha in ovariectomized females and a fivefold increase in plasma concentrations of tumor necrosis factor-alpha. Release of tumor necrosis factor-alpha and plasma concentrations were unchanged in proestrus mice under such conditions. When proestrus and ovariectomized animals were subjected to sepsis by cecal ligation and puncture at 24 hours after trauma-hemorrhage or sham operation, ovariectomized mice had a significantly higher death rate than proestrus mice. Conclusions: These findings suggest that female sex hormones play a critical role in maintaining immune responses after trauma-hemorrhage by suppressing the elaboration of tumor necrosis factor-alpha and prevent the increased lethality from subsequent sepsis. Thus, female sex hormones may be a useful adjunct in preventing trauma-induced immunodepression and increased susceptibility to subsequent sepsis.

AB - Objective: To determine whether reduction of circulating female sex hormones by ovariectomy causes suppression of macrophage (Mφ) function after trauma-hemorrhage and increases susceptibility to subsequent sepsis. Summary Background Data: Studies indicate that immune functions are markedly depressed in males but not in proestrus females after trauma-hemorrhage. Although male sex steroids are immunosuppressive, it remains unknown whether female sex hormones are immunoprotective after trauma-hemorrhage. Methods: Circulating female sex hormones were reduced by ovariectomy of 8-week-old female CBA/J mice. Two weeks afterward, ovariectomy and proestrus sham-ovariectomy mice were subjected to laparotomy (i.e., soft tissue trauma) and hemorrhagic shock (35 ± 5 mm Hg for 90 minutes, then resuscitated) or sham operation. Two hours afterward, splenic and peritoneal Mφ and Kupffer cells were isolated and cytokine production was assessed. In a second series of experiments, animals were subjected to sepsis by cecal ligation and puncture at 24 hours after trauma-hemorrhage or sham operation, and survival was assessed. Results: Release of interleukin-1 and interleukin-6 by splenic and peritoneal Mφ from proestrus mice was maintained after trauma-hemorrhage, whereas release of interleukin-1 and interleukin-6 by Mφ from ovariectomized mice was depressed by approximately 50%. In contrast, trauma-hemorrhage resulted in a fourfold increase of Kupffer cell release of tumor necrosis factor-alpha in ovariectomized females and a fivefold increase in plasma concentrations of tumor necrosis factor-alpha. Release of tumor necrosis factor-alpha and plasma concentrations were unchanged in proestrus mice under such conditions. When proestrus and ovariectomized animals were subjected to sepsis by cecal ligation and puncture at 24 hours after trauma-hemorrhage or sham operation, ovariectomized mice had a significantly higher death rate than proestrus mice. Conclusions: These findings suggest that female sex hormones play a critical role in maintaining immune responses after trauma-hemorrhage by suppressing the elaboration of tumor necrosis factor-alpha and prevent the increased lethality from subsequent sepsis. Thus, female sex hormones may be a useful adjunct in preventing trauma-induced immunodepression and increased susceptibility to subsequent sepsis.

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