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

Takao Suzuki, Tomoharu Shimizu, Huang Ping Yu, Ya Ching Hsieh, Mashkoor A. Choudhry, Martin G. Schwacha, Irshad H. Chaudry

Research output: Contribution to journalArticlepeer-review

43 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)163-168
Number of pages6
JournalJournal of applied physiology
Issue number1
StatePublished - Jan 2007
Externally publishedYes


  • Diarylpropionitrile
  • Kupffer cell
  • Macrophage
  • Peripheral blood mononuclear cell
  • Propyl pyrazole triol

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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