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. 2016 Oct;76(4):272-9.
doi: 10.1111/aji.12547. Epub 2016 Aug 1.

Inhibition of T-cell activation attenuates hypertension, TNFα, IL-17, and blood-brain barrier permeability in pregnant rats with angiogenic imbalance

Cynthia Bean  1 , Shauna-Kay Spencer  1 , Teylor Bowles  1 , Patrick B Kyle  2 , Jan M Williams  3 , Jacob Gibbens  1 , Kedra Wallace  4
Affiliations

Inhibition of T-cell activation attenuates hypertension, TNFα, IL-17, and blood-brain barrier permeability in pregnant rats with angiogenic imbalance

Cynthia Bean et al. Am J Reprod Immunol. 2016 Oct.

Abstract

Problem: Angiogenic imbalance during pregnancy is associated with immune activation, hypertension, increased T cell infiltration, and neurological insults.

Method of study: On gestational day (GD) 12, timed-pregnant rats were infused with anti-angiogenic factors sFlt-1 and sEndoglin (4.7 and 7 μg/kg) to create HELLP syndrome via mini-osmotic pumps for 8 days, with a subset of these rats having Orencia (2 mg/kg) infused on GD13. On GD19, blood-brain barrier (BBB) permeability was evaluated via Evan's Blue infusion, blood was collected for T-cell measurements, inflammatory cytokine secretion. Brain tissues were also collected to examine inflammatory cytokine infiltration.

Results: T-cell attenuation with Orencia decreased circulating CD4(+) and CD8(+) T cells, circulating tumor necrosis factor alpha (TNFα) and IL-17, BBB permeability and significantly decreased biochemical evidence of HELLP compared to untreated HELLP rats.

Conclusions: These data support the hypothesis that T cells have a critical role in contributing to the pathophysiology that is seen in angiogenic imbalance during pregnancy.

Keywords: CD4+ T cells; HELLP syndrome; TNFa; blood-brain barrier; hypertension, pregnancy brain.

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Figures

Figure 1
Figure 1. Blood brain barrier disruption and neuroinflammation in HELLP rats
Rats with HELLP syndrome had significantly more EB leakage into the posterior cortex and cerebellum/brainstem regions of the brain compared to normal pregnant rats (A). Administration of Orencia to HELLP rats significantly decreased EB leakage in the posterior cortex and cerebellum/brainstem compared to HELLP rats (A; n=6/group). Circulating CD4+ and CD8+ T cells were significantly increased in HELLP rats (n=5) compared to NP rats (n=6), but was decreased in response to Orencia (n=5; B). *p<0.05, **p<0.005, ***p<0.0005 between the indicated groups. # denotes statistical significance compared to NP+Orencia rats.
Figure 2
Figure 2. Orencia decreases the parameters of HELLP syndrome
HELLP rats (n=13) have increased lactate dehydrogenase (A), increased alanine aminotransferase (B), decreased platelet count (C), and increased mean arterial pressure (D) compared to NP rats (n=10). HELLP + Orencia rats (n=10) had significantly decreased hemolysis and liver enzymes compared to HELLP rats. Platelets were also significantly increased and mean arterial pressure was decreased in response to Orencia administration. *p <0.05, **p<0.005, ***p<0.0005 between indicated groups. # denotes statistical significance compared to NP+Orencia rats.
Figure 3
Figure 3. Orencia decreases circulating IL-17 and TNFα
Circulating IL-17, IL-6 and TNFα were increased in HELLP rats compared to NP rats. Orencia administration to either NP or HELLP rats decreased IL-17 and TNFα. **p<0.005, ***p<0.0005 between indicated groups. # indicates p<0.05 compared to NP+Orencia rats.
See this image and copyright information in PMC

References

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