Abstract 26: IL-17 Causes Hypertension, Reduced Fetal Weight And Natural Killer Cell Activation In The Absence Of T Cells

Abstract

Preeclampsia (PE) is characterized by new onset hypertension (HTN), intrauterine growth restriction (IUGR), multi-organ dysfunction, and is associated with increased inflammatory cytokines, such as interleukin 17 (IL-17). More recent studies demonstrate a role for mitochondrial (mt) dysfunction/mtROS in the pathogenesis of PE. Although we have shown T helper cells from a rat model of PE cause HTN and mt dysfunction the causative factors for mt dysfunction are still being identified. In addition, we have shown that IL-17 cause HTN, IUGR and activate natural killer (NK) cells, and cause mt dysfunction in pregnant Sprague Dawley rats. However, in our previous studies we couldn’t differentiate the effect of activated TH cells versus IL-17 to cause these characteristics of PE. The athymic nude rat model lacks mature T cells but does have other components of the immune system, and will thus allow us to examine the role of IL-17 in the absence of TH cells in the pathophysiology of PE. We hypothesize that in the absence of T cells IL-17 induces HTN, NK cell activation and IUGR which is associated with renal and placental mt dysfunction during pregnancy. To test our hypothesis, IL-17 (150 pg/day) was infused via osmotic minipumps inserted on gestation day (GD) 14. Blood pressure (MAP) and mt function were measured on GD19 and were compared to untreated pregnant (NP) athymic nude rats. In response to IL-17; MAP increased from 95±4mmHg in NP(n=6) to 115±2 in NP+IL-17(n=6) (p<0.001); pup weight decreased from 1.46±0.2 g in NP (n=6) to 0.98±0.07g in NP+IL-17 (n=6) (p<0.05); NK cell activation increased from 0±0 %lymphocytes in NP (n=3) to 0.4±0.1% lymphocytes in NP+IL-17 rats (n=6). Interestingly, placental mtROS reduced 54% fold compared to NP and renal mtROS reduced 51.2% compared to NP. ATP production increased from 15.53±1.6 pmol of O2/sec/mg in NP (n=3) to 105.5±91 pmol of O2/sec/mg in NP+IL-17 (n=3) in the placenta, and from 1196±460 pmol of O2/sec/mg in NP (n=4) to 2016±951 pmol of O2/sec/mg NP+IL17 (n=4) in the kidney. These results show that although IL-17 induces HTN, IUGR, and NK cell activation independent of T cells, T cells are necessary for reduced mitochondrial function observed in PE and in rat models of placental ischemia.