Low Dose of IL-2 Normalizes Hypertension and Mitochondrial Function in the RUPP Rat Model of Placental Ischemia
IL-2 is a cytokine released from CD4+T cells with dual actions and can either potentiate the inflammatory response or quell a chronic inflammatory response depending on its circulating concentration. IL-2 is elevated in many chronic inflammatory conditions and is increased during preeclampsia (PE)....
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MDPI AG
2021-10-01
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| Online Access: | https://www.mdpi.com/2073-4409/10/10/2797 |
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| author | Evangeline Deer Lorena M. Amaral Nathan Campbell Sarah Fitzgerald Owen Herrock Tarek Ibrahim Babbette LaMarca |
| author_facet | Evangeline Deer Lorena M. Amaral Nathan Campbell Sarah Fitzgerald Owen Herrock Tarek Ibrahim Babbette LaMarca |
| author_sort | Evangeline Deer |
| collection | DOAJ |
| description | IL-2 is a cytokine released from CD4+T cells with dual actions and can either potentiate the inflammatory response or quell a chronic inflammatory response depending on its circulating concentration. IL-2 is elevated in many chronic inflammatory conditions and is increased during preeclampsia (PE). PE is characterized by new-onset hypertension during pregnancy and organ dysfunction and increasing evidence indicates that proinflammatory cytokines cause hypertension and mitochondrial (mt) dysfunction during pregnancy. The reduced uterine perfusion pressure (RUPP) model of placental ischemia is a rat model of PE that we commonly use in our laboratory and we have previously shown that low doses of recombinant IL-2 can decrease blood pressure in RUPP rats. The objective of this study was to determine the effects of a low dose of recombinant IL-2 on multi-organ mt dysfunction in the RUPP rat model of PE. We tested our hypothesis by infusing recombinant IL-2 (0.05 ng/mL) into RUPP rats on GD14 and examined mean arterial pressure (MAP), renal, placental and endothelial cell mt function compared to control RUPP. MAP was elevated in RUPP rats (<i>n</i> = 6) compared to controls (<i>n =</i> 5) (122 ± 5 vs. 102 ± 3 mmHg, <i>p</i> < 0.05), but was reduced by administration of LD recombinant IL-2 (107 ± 1 vs. 122 ± 5 mmHg, <i>n =</i> 9, <i>p</i> < 0.05). Renal, placental and endothelial mt ROS were significantly increased in RUPP rats compared to RUPP+ IL-2 and controls. Placental and renal respiration rates were reduced in RUPP rats compared to control rats but were normalized with IL-2 administration to RUPPs. These data indicate that low-dose IL-2 normalized multi-organ mt function and hypertension in response to placental ischemia. |
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| series | Cells |
| spelling | doaj.art-0843f3705248410a8834db4fb71f6dfc2023-11-22T17:49:17ZengMDPI AGCells2073-44092021-10-011010279710.3390/cells10102797Low Dose of IL-2 Normalizes Hypertension and Mitochondrial Function in the RUPP Rat Model of Placental IschemiaEvangeline Deer0Lorena M. Amaral1Nathan Campbell2Sarah Fitzgerald3Owen Herrock4Tarek Ibrahim5Babbette LaMarca6Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USADepartment of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USADepartment of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USADepartment of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USADepartment of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USADepartment of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USADepartment of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USAIL-2 is a cytokine released from CD4+T cells with dual actions and can either potentiate the inflammatory response or quell a chronic inflammatory response depending on its circulating concentration. IL-2 is elevated in many chronic inflammatory conditions and is increased during preeclampsia (PE). PE is characterized by new-onset hypertension during pregnancy and organ dysfunction and increasing evidence indicates that proinflammatory cytokines cause hypertension and mitochondrial (mt) dysfunction during pregnancy. The reduced uterine perfusion pressure (RUPP) model of placental ischemia is a rat model of PE that we commonly use in our laboratory and we have previously shown that low doses of recombinant IL-2 can decrease blood pressure in RUPP rats. The objective of this study was to determine the effects of a low dose of recombinant IL-2 on multi-organ mt dysfunction in the RUPP rat model of PE. We tested our hypothesis by infusing recombinant IL-2 (0.05 ng/mL) into RUPP rats on GD14 and examined mean arterial pressure (MAP), renal, placental and endothelial cell mt function compared to control RUPP. MAP was elevated in RUPP rats (<i>n</i> = 6) compared to controls (<i>n =</i> 5) (122 ± 5 vs. 102 ± 3 mmHg, <i>p</i> < 0.05), but was reduced by administration of LD recombinant IL-2 (107 ± 1 vs. 122 ± 5 mmHg, <i>n =</i> 9, <i>p</i> < 0.05). Renal, placental and endothelial mt ROS were significantly increased in RUPP rats compared to RUPP+ IL-2 and controls. Placental and renal respiration rates were reduced in RUPP rats compared to control rats but were normalized with IL-2 administration to RUPPs. These data indicate that low-dose IL-2 normalized multi-organ mt function and hypertension in response to placental ischemia.https://www.mdpi.com/2073-4409/10/10/2797hypertensionpreeclampsiaIL-2inflammationoxidative stressplacental ischemia |
| spellingShingle | Evangeline Deer Lorena M. Amaral Nathan Campbell Sarah Fitzgerald Owen Herrock Tarek Ibrahim Babbette LaMarca Low Dose of IL-2 Normalizes Hypertension and Mitochondrial Function in the RUPP Rat Model of Placental Ischemia Cells hypertension preeclampsia IL-2 inflammation oxidative stress placental ischemia |
| title | Low Dose of IL-2 Normalizes Hypertension and Mitochondrial Function in the RUPP Rat Model of Placental Ischemia |
| title_full | Low Dose of IL-2 Normalizes Hypertension and Mitochondrial Function in the RUPP Rat Model of Placental Ischemia |
| title_fullStr | Low Dose of IL-2 Normalizes Hypertension and Mitochondrial Function in the RUPP Rat Model of Placental Ischemia |
| title_full_unstemmed | Low Dose of IL-2 Normalizes Hypertension and Mitochondrial Function in the RUPP Rat Model of Placental Ischemia |
| title_short | Low Dose of IL-2 Normalizes Hypertension and Mitochondrial Function in the RUPP Rat Model of Placental Ischemia |
| title_sort | low dose of il 2 normalizes hypertension and mitochondrial function in the rupp rat model of placental ischemia |
| topic | hypertension preeclampsia IL-2 inflammation oxidative stress placental ischemia |
| url | https://www.mdpi.com/2073-4409/10/10/2797 |
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