Salutary effects of 17beta-estradiol on Peyer's patch T cell functions following trauma-hemorrhage

Although 17beta-estradiol (E2) administration following trauma-hemorrhage (T-H) improves immune functions in male rodents, it remains unclear whether E2 has salutary effects on Peyer's patch (PP) T cell functions. We hypothesized that T-H induces PP T cell dysfunction and E2 administration following T-H will improve PP T cell function. T-H was induced in male C3H/HeN mice (6-8weeks) by midline laparotomy and approximately 90min of hemorrhagic shock (blood pressure 35mmHg), followed by fluid resuscitation (4x the shed blood volume in the form of Ringer's lactate). Estrogen receptor (ER)-alpha agonist propyl pyrazole triol (PPT; 5microg/kg), ER-beta agonist diarylpropionitrile (DPN; 5microg/kg), E2 (50microg/kg), or vehicle was injected subcutaneously at resuscitation onset. Two hours later, mice were sacrificed and PP T cells isolated. PP T cell capacity to produce cytokines in response to in vitro stimulation, PP T cell proliferation and MAPK (p38, ERK-1/2, JNK) activation were measured. Results indicate PP T cell proliferation, cytokine production and MAPK activation decreased significantly following T-H. E2, PPT or DPN administration normalized these parameters. Since PPT or DPN administration following T-H was effective in normalizing PP T cell functions, the salutary effects of E2 are mediated via ER-alpha and ER-beta.