Vesna D. Garovic
Editor of Hypertension in Pregnancy
Mayo Clinic, Rochester, USA
Dear Professor Garovic,
We have read the article ‘Tumor necrosis factor alpha (TNF-α) blockade improves natural killer cell (NK) activation, hypertension, and mitochondrial oxidative stress in a preclinical rat model of preeclampsia’ by Cunningham et al. published in Hypertension in Pregnancy 39:4, 399-404. We would like to congratulate the authors on this interesting paper.
In the article by Cunningham et al., the investigators show that treatment of the RUPP model of preeclampsia with the TNF-α blocker etanercept at gestational day 18 resulted in normalising key pathology associated with the disease, as well as reducing the amount of activated circulating and tissue natural killer cells. We would like to draw the author’s attention to our own study (Role of Tumor Necrosis Factor-α and Natural Killer Cells in Uterine Artery Function and Pregnancy Outcome in the Stroke-Prone Spontaneously Hypertensive Rat by Small et al. Hypertension. 2016; 68:1298–1307), where we showed that treatment of the SHRSP model of maternal chronic hypertension with etanercept reversed many of the pathological features of this model and, most relevant here, reduced the number of cytotoxic natural killer cells in the circulation and placenta.
The purpose of our letter is to highlight that a common effect of TNF-α blockade on natural killer cell accumulation and activation has been demonstrated in two preclinical models that capture the moderate and severe phenotypes of hypertensive complications of pregnancy. We suggest that the findings of Cunningham et al. should be taken in context with the consideration that preeclampsia is not an entity in itself but part of a spectrum; a school of thought that has been established by many key opinion leaders in the field. It is well known that pre-existing hypertension (such as that seen in the SHRSP model) is a major risk factor for the development of preeclampsia and, in turn, the occurrence of preeclampsia itself predisposes the woman to an increased risk of cardiovascular complications later in life. To our knowledge, investigation into the relationship between TNF-α and NK cells has not been conducted in women with hypertensive complications of pregnancy and we hypothesise that this could be a very valuable study indeed.
Yours faithfully,
Heather Y. Small Christian Delles
[email protected] [email protected]
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