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

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