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

Center for Surgical Research and Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama

Submitted 31 August 2006 ; accepted in final form 1 October 2006

Although 17-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)- or ER-. Accordingly, we examined which ER subtype predominantly mediates the salutary effects of 17-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- agonist propyl pyrazole triol (PPT; 5 µg/kg), the ER- agonist diarylpropionitrile (DPN; 5 µg/kg), 17-estradiol (50 µg/kg), or vehicle (10% DMSO) was injected subcutaneously during resuscitation, and various measurements were made 24 h thereafter. 17-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- production by Kupffer cells increased; however, splenic macrophages (SM), alveolar macrophages (AM), 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 17-estradiol following trauma-hemorrhage prevented all of these alterations. PPT had the same effects as 17-estradiol on IL-6 and TNF- production by Kupffer cells and SM, and DPN had the same effects on AM and PBMC. The same effects as 17-estradiol on IL-10 production were observed by PPT on Kupffer cells and DPN on PBMC. Both agonists were equally effective on SM and AM. Thus ER subtypes have tissue compartment-specific roles in mediating the effects of 17-estradiol on immune cell functions following trauma-hemorrhage.

Kupffer cell; macrophage; peripheral blood mononuclear cell; propyl pyrazole triol; diarylpropionitrile

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