Immunosuppression Improves Blood Pressure and Endothelial Function in a Rat Model of Pregnancy-Induced Hypertension

BACKGROUND Hypertensive disorders of pregnancy, including preeclampsia (PE), affect similar to 7-10% of pregnancies in the US. Clinical and experimental studies strongly suggest that the maternal immune system plays a role in the development of these disorders; however, few therapeutic options exist aside from delivery. METHODS Using a deoxycorticosterone acetate (DOCA)/salt-low renin rat model, which exhibits hypertension, proteinuria, endothelial dysfunction, and intrauterine growth restriction (IUGR), we measured serum cytokine levels as an indication of immune system activation. In addition, we suppressed the immune system with either azathioprine (Aza) or mycophenolate mofetil (MMF) during the second half of pregnancy to determine whether the these symptoms could be ameliorated. RESULTS Our results demonstrate that serum T helper-1 (Th1)-type inflammatory cytokines interleukin (IL)-2, IL-12, interferon-gamma (IFN gamma), and RANTES were significantly elevated in hypertensive pregnant rats while the Th2-type cytokine IL-4 was elevated in normal pregnant animals. Either Aza or MMF significantly attenuated the hypertension, proteinuria, and endothelial dysfunction as well as the increased proinflammatory Th1 cytokine profile in pregnant rats treated with DOCA/salt, and had no effect on these parameters in normal pregnant rats. CONCLUSION These data strongly suggest that maternal immune system activation plays a role in the development of pregnancy-induced hypertension (PIH).