Circulating Levels of Immunoreactive Cytokines in Women with Preeclampsia

Conrad, Kirk P.; Miles, Theresa M.; Benyo, Deborah Fairchild

doi:10.1111/j.1600-0897.1998.tb00398.x

Cited by 376 publications

(297 citation statements)

References 38 publications

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“…It has been hypothesized that placental ischemia and hypoxia during late pregnancy may contribute to maternal endothelial cell dysfunction by enhancing the synthesis of cytokines such as TNF-␣ (12,14). In support of the cytokine hypothesis, several studies have shown increased plasma levels of TNF-␣ during preeclampsia (14,39,66,70). However, some studies have shown no change in plasma TNF-␣ levels in preeclamptic women (22,29).…”

Section: Discussionmentioning

confidence: 99%

“…Studies in animal models of PIH have proposed that a localized reduction in the uteroplacental perfusion pressure and the ensuing placental ischemia and hypoxia during late pregnancy trigger the release of vasoactive factors from the ischemic placenta into the systemic circulation, and that the released factors in turn cause systemic vascular changes and lead to increased vascular resistance and PIH (3, 7, 11-17, 21, 35, 41, 47). Although several placental factors have been suggested, a key role for plasma cytokines in the pathogenesis of PIH has been hypothesized (12,14,39,66). …”

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confidence: 99%

“…Although several placental factors have been suggested, a key role for plasma cytokines in the pathogenesis of PIH has been hypothesized (12,14,39,66). In support of the "cytokine hypothesis," it has been shown that the plasma levels of tumor necrosis factor-␣ (TNF-␣) are elevated in women with preeclampsia (14,39,66). Also, we have shown that a two-to threefold elevation in plasma TNF-␣ in late-pregnancy rats results in significant increases in systemic vascular resistance and arterial pressure (2,19,27).…”

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confidence: 99%

“…Although studies in TNF-␣-infused pregnant rats have suggested a possible association between the endothelial cell dysfunction and the hypertension (19), it is not clear whether the reduction in endotheliumdependent vascular relaxation is caused by TNF-␣ or whether it is merely a consequence of the hypertension that is developed during chronic TNF-␣ infusion. Also, other cytokines such as interleukin 6 (IL-6), which is activated by TNF-␣, have been shown to be elevated in the plasma of preeclamptic women (14,29,66), which raises the possibility that the chronic vascular effects of TNF-␣ may not be caused directly by TNF-␣ but rather by another cytokine. This made it necessary to investigate the direct effects of TNF-␣ on the mechanisms of vascular reactivity in systemic vessels during late gestation.…”

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confidence: 99%

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TNF-α enhances contraction and inhibits endothelial NO-cGMP relaxation in systemic vessels of pregnant rats

Giardina

Green

Cockrell

et al. 2002

American Journal of Physiology-Regulatory, Integrative and Comp

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. TNF-␣ enhances contraction and inhibits endothelial NO-cGMP relaxation in systemic vessels of pregnant rats. Am J Physiol Regulatory Integrative Comp Physiol 283: R130-R143, 2002. First published February 28, 2002 10.1152/ajpregu.00704. 2001.-Tumor necrosis factor-␣ (TNF-␣) is elevated in the plasma of preeclamptic women and may have a role in pregnancy-induced hypertension. However, whether the hemodynamic effects of TNF-␣ reflect the direct effects on vascular reactivity is unclear. We tested the hypothesis that TNF-␣ impairs endothelium-dependent relaxation and enhances vascular contraction in systemic vessels of pregnant rats. We measured isometric contraction in aortic strips isolated from virgin and pregnant Sprague-Dawley rats (nontreated vs. treated for 2 h with 10-1,000 pg/ml TNF-␣). In endotheliumintact vascular strips, TNF-␣ caused greater enhancement of phenylephrine (Phe) contraction in pregnant than virgin rats. TNF-␣ caused significant inhibition of ACh-and bradykinin-induced vascular relaxation and nitrite/nitrate production that were more prominent in pregnant than virgin rats. N G -nitro-L-arginine methyl ester [L-NAME, 100 M, an inhibitor of nitric oxide (NO) synthase] or 1H-[1,2,4]oxadiazolo[4,3]-quinoxalin-1-one (ODQ, 1 M, an inhibitor of cGMP production in smooth muscle) inhibited ACh relaxation and enhanced Phe contraction in nontreated but to a lesser extent in TNF-␣-treated vessels, particularly those of pregnant rats. Endothelium removal enhanced Phe contraction in nontreated but not TNF-␣-treated vessels, especially those of pregnant rats. Relaxation of Phe contraction with the NO donor sodium nitroprusside was not different between nontreated and TNF-␣-treated vessels. Thus TNF-␣ enhances vascular contraction and inhibits endothelium-dependent NO-cGMP-mediated vascular relaxation in systemic vessels, particularly those of pregnant rats. The results support a direct role for TNF-␣ as a possible mediator of increased vascular resistance associated with pregnancy-induced hypertension.cytokines; endothelium; nitric oxide; pregnancy; arterial pressure; tumor necrosis factor-␣ NORMAL PREGNANCY IS OFTEN associated with decreased systemic vascular resistance and arterial pressure and reduced vascular reactivity to circulating vasoconstrictors (20,35,46,51). The hemodynamic and vascular changes associated with normal pregnancy have been attributed in part to increased nitric oxide (NO) synthesis by various cells including the vascular endothelial cells (1,18,54,62,69). This is supported by studies showing that the tissue expression and activity of NO synthase (NOS) are enhanced during late gestation (4,13,61,68) and that the metabolic production and plasma level of guanosine 3Ј,5Ј-cyclic monophosphate (cGMP), a second messenger of NO and a cellular mediator of vascular smooth muscle relaxation (30,34), are increased during pregnancy (15).In 5-10% of pregnancies, women develop a condition called preeclampsia, which is characterized by proteinuria, increased intravascular coagulation and sy...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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TNF-α enhances contraction and inhibits endothelial NO-cGMP relaxation in systemic vessels of pregnant rats

Giardina

Green

Cockrell

et al. 2002

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Some researchers hypothesized that the inadequate remodeling of uterine arteries characteristic of preeclampsia is responsible for the focal ischemia and generation of pro inflammatory cytokines such as Interleukin-6 (IL-6) and tumor nrcrosis factor a (TNF-a) by the placenta [7][8][9]. IL-6 enhances endothelial cell permeability, aberrant angiogenesis and inhibits prostacyclin synthesis thereby modifying vascular physiology profoundly [10].…”

Section: Introductionmentioning

confidence: 99%

Association of Inflammatory Cytokines, Lipid Peroxidation End Products and Nitric Oxide with the Clinical Severity and Fetal Outcome in Preeclampsia in Indian Women

Tayal¹,

Goswami

Patra

et al. 2013

Ind J Clin Biochem

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Preeclampsia is a multisystem disorder associated with maternal hypertension, placental abnormalities and adverse fetal outcomes. The various pathways involved in its etiology include endothelial dysfunction, inflammatory milieu, lipid peroxidation and immunological imbalance. The present study was conducted to evaluate the causative and predictive role of nitric oxide, lipid peroxidation end products (MDA) and inflammatory cytokines (IL-6, TNF-a) in clinical presentation, severity and fetal outcome in preeclampsia. The study population was divided into 3 groups-Non-pregnant females comprising the control population; G1 and G2 groups included normal pregnant and pregnant females with preeclampsia with 50 patients in each group. Nitric Oxide and MDA levels were found to be highest in the preeclamptic patients as compared to other two groups. ROC curve analysis shows the superiority of the inflammatory markers as determinants of severity of preeclampsia which suggests the emerging role of pro inflammatory markers in the various pathological changes in preeclampsia. TNF-a emerged as the best marker in multivariate analysis and thus, has the potential for being used as a marker for PIH. Our study illustrates the multifactorial etiology of preeclampsia involving oxidative stress, proinflammatory milieu and endothelial dysfunction.

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C‐C motif chemokine ligand 23 abolishes ER stress‐ and LPS‐induced reduction in proliferation of bovine endometrial epithelial cells

Lim

Bae

Bazer

et al. 2017

Journal Cellular Physiology

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To reduce embryonic losses in domestic animals for economic production of livestock meat and milk, chemokines and their receptors are required for proper implantation and placentation during early pregnancy. In this study, we investigated the effects of C-C-motif chemokine ligand 23 (CCL23) on the proliferation of bovine endometrial (BEND) epithelial cells. CCL23 treatment improved BEND cell proliferation by enhancing PCNA and cyclin D1 expression via activation of the PI3K/AKT and MAPK signaling pathways. In addition, a combination of CCL23 and tunicamycin reversed the ER stress-induced reduction in cell proliferation and the decreased expression of UPR-mediated signaling proteins, including IRE1α, PERK, and ATF6α. Moreover, it regulated the lipopolysaccharide-induced inflammation in BEND cells by inhibiting the expression of pro-inflammatory cytokines (IL-6 and IL-8), and by restoring intracellular Ca levels. These findings demonstrate that CCL23 improves endometrial development and uterine receptivity required for implantation and placentation during early pregnancy.

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Circulating Levels of Immunoreactive Cytokines in Women with Preeclampsia

Abstract: Elevated levels of TNF-alpha and IL-6 may contribute to the putative endothelial dysfunction of preeclampsia.

Cited by 376 publications

References 38 publications

TNF-α enhances contraction and inhibits endothelial NO-cGMP relaxation in systemic vessels of pregnant rats

TNF-α enhances contraction and inhibits endothelial NO-cGMP relaxation in systemic vessels of pregnant rats

Association of Inflammatory Cytokines, Lipid Peroxidation End Products and Nitric Oxide with the Clinical Severity and Fetal Outcome in Preeclampsia in Indian Women

C‐C motif chemokine ligand 23 abolishes ER stress‐ and LPS‐induced reduction in proliferation of bovine endometrial epithelial cells

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