TNF-α Inhibition Improves Blood Pressure and Inflammation in Response to Adoptive Transfer of Preeclamptic T Helper Cells

Preeclampsia (PE) is new-onset hypertension with chronic inflammation and systemic endothelial dysfunction after the 20th week of pregnancy. We’ve shown that CD4+ T helper cells contribute to PE phenotype through production of proinflammatory cytokines such as TNF-α. We have previously shown that etanercept, a soluble TNF-α inhibitor, improves the PE phenotype in RUPP rats. Therefore, we hypothesize that etanercept will improve blood pressure, endothelial function, and inflammation in response to the adoptive transfer of placental PE CD4+ T cells into pregnant athymic nude rats. Placental CD4+ T cells were isolated from normal pregnant (NP) and PE patients following delivery. One million CD4+ T cells were injected I.P. into athymic nude rats on gestational day (GD) 12. Etanercept (0.4 mg/kg) was given as an I.P. injection on GD 15. Carotid catheters were implanted on GD 18. Blood pressure (MAP) was measured on GD 19. Preproendothelin expression, measured by RT-PCR, and ET-1 and TNF-α were measured with ELISA. A one-way ANOVA was used for statistical analysis. MAP increased with PE CD4+ T cells to 120±3 mmHg, n=17, p< 0.05, compared to NP CD4+ T cells (102±4 mmHg, n=12), which was blunted with Etanercept (110±3 mmHg, n=8). Renal ET-1 was lower in Etanercept treated rats (1.6±034, n=7) compared to PE recipients (3.4±0.4 pg/mg protein). Placental ET-1 was significantly increased with PE CD4+T cells (20.4±0.7, n=4) compared to NP CD4+ T cells (13.6±2.4, n=5) or Etanercept treated rats (10.8±1.0 pg/mg protein, n=5). Renal TNF-α was significantly increased with PE CD4+ T cells (3.9±0.3, n=7) compared to NP recipients (3.1±0.2 pg/mg protein, n=6) and PE CD4+ T cells recipients treated with Etanercept (1.3±0.2 pg/mg protein, n=8). TNF-α blockade with Etanercept lowers blood pressure and multiorgan ET-1, a marker of endothelial dysfunction and a hallmark of PE, in response to adoptive transfer of preeclamptic CD4+ T cells. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.