Tumor necrosis factor α induces a model of preeclampsia in pregnant baboons (Papio hamadryas)

Neroli S. Sunderland, Sally E. Thomson, Scott J. Heffernan, Shirlene Lim, John Thompson, Robert Ogle, Paul McKenzie, Paul J. Kirwan, Angela Makris, Annemarie Hennessy

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Preeclampsia is a common disease of pregnancy characterised by maternal hypertension and proteinuria. Abnormal placentation in early pregnancy and abnormal cytokine and anti-angiogenic factor expression are thought to contribute to the clinical syndrome of endothelial dysfunction evident in the second half of gestation. The mechanisms underlying both the placental pathology and its translation to the maternal clinical syndrome are not fully understood. A model of preeclampsia manifest by clinically evident endothelial dysfunction (increased blood pressure and proteinuria) was induced by administration of low-dose TNF-alpha for 2 weeks at mid-gestation in pregnant baboons (Papio hamadryas). Blood pressure was monitored continuously and remotely by intra-arterial radiotelemetry. Following TNF-alpha infusion, there was an increase in systolic and diastolic blood pressure and development of proteinuria in pregnant treated animals, but not in pregnant saline controls nor in non-pregnant TNF-alpha treated animals. The treated pregnant animals also developed elevated plasma soluble FMS-like tyrosine kinase-1 (5FLT-1) and increased placental mRNA expression of sFLT-1 and soluble endoglin (sEng). These results clearly demonstrate that the cytokine TNF-alpha can induce the clinical and biochemical features of human preeclampsia. The results identify a link between cytokines, placental dysfunction and endothelial dysfunction resulting in a loss of maternal blood pressure control. (C) 2011 Elsevier Ltd. All rights reserved.

LanguageEnglish
Pages192-199
Number of pages8
JournalCytokine
Volume56
Issue number2
DOIs
Publication statusPublished - Nov 2011
Externally publishedYes

Keywords

  • Tumor necrosis factor alpha
  • Non-human primates
  • Preeclampsia
  • Animal models
  • Pregnancy

Cite this

Sunderland, N. S., Thomson, S. E., Heffernan, S. J., Lim, S., Thompson, J., Ogle, R., ... Hennessy, A. (2011). Tumor necrosis factor α induces a model of preeclampsia in pregnant baboons (Papio hamadryas). Cytokine, 56(2), 192-199. https://doi.org/10.1016/j.cyto.2011.06.003
Sunderland, Neroli S. ; Thomson, Sally E. ; Heffernan, Scott J. ; Lim, Shirlene ; Thompson, John ; Ogle, Robert ; McKenzie, Paul ; Kirwan, Paul J. ; Makris, Angela ; Hennessy, Annemarie. / Tumor necrosis factor α induces a model of preeclampsia in pregnant baboons (Papio hamadryas). In: Cytokine. 2011 ; Vol. 56, No. 2. pp. 192-199.
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Sunderland, NS, Thomson, SE, Heffernan, SJ, Lim, S, Thompson, J, Ogle, R, McKenzie, P, Kirwan, PJ, Makris, A & Hennessy, A 2011, 'Tumor necrosis factor α induces a model of preeclampsia in pregnant baboons (Papio hamadryas)' Cytokine, vol. 56, no. 2, pp. 192-199. https://doi.org/10.1016/j.cyto.2011.06.003

Tumor necrosis factor α induces a model of preeclampsia in pregnant baboons (Papio hamadryas). / Sunderland, Neroli S.; Thomson, Sally E.; Heffernan, Scott J.; Lim, Shirlene; Thompson, John; Ogle, Robert; McKenzie, Paul; Kirwan, Paul J.; Makris, Angela; Hennessy, Annemarie.

In: Cytokine, Vol. 56, No. 2, 11.2011, p. 192-199.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Thompson,John

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AU - McKenzie,Paul

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AB - Preeclampsia is a common disease of pregnancy characterised by maternal hypertension and proteinuria. Abnormal placentation in early pregnancy and abnormal cytokine and anti-angiogenic factor expression are thought to contribute to the clinical syndrome of endothelial dysfunction evident in the second half of gestation. The mechanisms underlying both the placental pathology and its translation to the maternal clinical syndrome are not fully understood. A model of preeclampsia manifest by clinically evident endothelial dysfunction (increased blood pressure and proteinuria) was induced by administration of low-dose TNF-alpha for 2 weeks at mid-gestation in pregnant baboons (Papio hamadryas). Blood pressure was monitored continuously and remotely by intra-arterial radiotelemetry. Following TNF-alpha infusion, there was an increase in systolic and diastolic blood pressure and development of proteinuria in pregnant treated animals, but not in pregnant saline controls nor in non-pregnant TNF-alpha treated animals. The treated pregnant animals also developed elevated plasma soluble FMS-like tyrosine kinase-1 (5FLT-1) and increased placental mRNA expression of sFLT-1 and soluble endoglin (sEng). These results clearly demonstrate that the cytokine TNF-alpha can induce the clinical and biochemical features of human preeclampsia. The results identify a link between cytokines, placental dysfunction and endothelial dysfunction resulting in a loss of maternal blood pressure control. (C) 2011 Elsevier Ltd. All rights reserved.

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