Tissue compartment-specific role of estrogen receptor subtypes in immune cell cytokine production following trauma-hemorrhage

Academic Article


  • Although 17β-estradiol administration following trauma-hemorrhage attenuates plasma cytokines and alteration in immune cell cytokine production, it is not known whether the salutary effects are mediated via estrogen receptor (ER)-α or ER-β. Accordingly, we examined which ER subtype predominantly mediates the salutary effects of 17β-estradiol on systemic inflammatory response/immune cell cytokine production in various tissues following trauma-hemorrhage. Male rats underwent trauma-hemorrhage (mean blood pressure: 40 mmHg for 90 min) and fluid resuscitation. The ER-α agonist propyl pyrazole triol (PPT; 5 μg/kg), the ER-α agonist diarylpropionitrile (DPN; 5 μg/kg), 17β-estradiol (50 μg/kg), or vehicle (10% DMSO) was injected subcutaneously during resuscitation, and various measurements were made 24 h thereafter. 17β-Estradiol or PPT administration following trauma-hemorrhage prevented the increase in plasma IL-6 and IL-10 levels that were observed in vehicle-treated animals. IL-6 and TNF-α production by Kupffer cells increased; however, splenic macrophages (SMΦ), alveolar macrophages (AMΦ), and peripheral blood mononuclear cells (PBMC) had decreased release of these cytokines after trauma-hemorrhage. IL-10 production, however, increased in all macrophage populations. Administration of 17β-estradiol following trauma-hemorrhage prevented all of these alterations. PPT had the same effects as 17β-estradiol on IL-6 and TNF-α production by Kupffer cells and SMΦ, and DPN had the same effects on AMΦ and PBMC. The same effects as 17β-estradiol on IL-10 production were observed by PPT on Kupffer cells and DPN on PBMC. Both agonists were equally effective on SMΦ and AMΦ. Thus ER subtypes have tissue compartment-specific roles in mediating the effects of 17β-estradiol on immune cell functions following trauma-hemorrhage. Copyright © 2007 the American Physiological Society.
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    Author List

  • Suzuki T; Shimizu T; Yu HP; Hsieh YC; Choudhry MA; Schwacha MG; Chaudry IH
  • Start Page

  • 163
  • End Page

  • 168
  • Volume

  • 102
  • Issue

  • 1