Abstract
Objective
We examined the hypothesis tha fetal proinflammatory cytokine release is a feature of placental vascular disease causing fetal compromise. We measured the concentrations of fetal proinflammaory cytokines interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and interleukin-8 (IL-8) in the presence of vascular disease in the umbilical placental villous circulation. Vascular disease was identified by high-resistance umbilical artery Doppler flow velocity waveform studies.
Methods
We measured levels of the inflammatory cytokines IL-6 and TNF-α and the chemokine IL-8 in fetal blood. Blood was collected from the umbilical vein at delivery, and serumwas stored at −70C until assayed using chemiluminescent and enzyme-linked immunosorbent assay methods. We studied 36 normal pregnancies delivered by elective cesarean at term and 50 pregnancies with a high-resistance umbilical artery Doppler flow velocity waveform pattern indicative of feal placental vascular disease delivered by elective cesarean because of potential fetal compromise.
Results
In the presence of umbilical placental vascular disease there were significantly higher levels of IL-6 (median 5.3 pg/mL, P < .05) and IL-8 (median 26.5 pg/mL, P < .01) compared with normal pregnanices (median value of IL-6 and IL-8 were below assay threshold). There was no difference for TNF-α, with the median results undetectable in both groups.
Conclusion
We found higher concentrations of IL-6 and IL-8 in the fetal circulation in the presence of umbilical placental vascular disease.
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References
Lowry SF. Cytokine mediators of immunity and inflammation. Arch Surg 1993;128:1235–41.
Balkwill F. Cytokine amplification and inhibition of immune and inflammatory responses. J Viral Hepatol 1997;4:6–15.
Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 1999;340:448–54.
Wardle EN. Cytokines: An overview. Eur J Med 1993;2:617–23.
Cotran RS, Pober JS. Cytokine-endothelial interactions in inflammation, immunity, and vascular injury. J Am Soc Nephrol 1990;1:225–35.
Gerard C, Rollins BJ. Chemokines and disease. Nat Immunol 2000;2:108–15.
Fox H. The histopathology of placental insufficiency. J Clin Path 1976;29:(Suppl 10)1–8.
Rankin JH, McLaughlin MK. The regulation of the placental blood flows. J Dev Physiol 1979;1:3–30.
Trudinger BJ, Giles WB, Cook CM. Flow velocity waveforms in the maternal uteroplacental and fetal umbilical placental circulations. Am J Obstet Gynecol 1985;152:155–63.
Giles WB, Trudinger BJ, Baird PJ. Fetal umbilical artery flow velocity waveforms and placental resistance: Pathological correlation. Br J Obstet Gynaecol 1985;92:31–8.
Hitschold T, Weiss E, Beck T, Hunterfering H, Berle P. Low target birth weight or growth retardation? Umbilical Doppler flow velocity waveforms and histometric analysis of fetoplacental vascular tree. Am J Obstet Gynecol 1993;168:1260–4.
Salafia CM, Pezzullo JC, Minior VK, Divon MY. Placental pathology of absent and reversed end-diastolic flow in growth-restricted fetuses. Obstet Gynecol 1997;90:830–6.
Salafia CM, Minior VK, Pezzullo JC, Popek EJ, Rosenkrantz TS, Vintzileos AM. Intrauterine growth restriction in infants of less than thirty-two weeks’ gestation: Associated placental pathologic features. Am J Obstet Gynecol 1995;173:1049–57.
Wang X, Athayde N, Trudinger BJ. Endothelial cell expression of cell adhesion molecules is induced by fetal plasma from pregnancy with umbilical placental vascular disease. Br J Obstet Gynecol 2002. In press.
Wang X, Yi SN, Athayde N, Trudinger BJ. Endothelial cell apoptosis is induced by fetal plasma from pregnancy with umbilical placental vascular disease and mediated by caspase. Am J Obstet Gynecol 2002;186:557–63.
Wang X, Wang J, Trudinger BJ. Gene expression of nitric oxide synthase by human umbilical vein endothelial cells. J Soc Gynecol Investig 2001;7:107A.
Karsdorp VH, Dekker GA, Bast A, et al. Maternal and fetal plasma concentrations of endothelin, lipidhydroperoxides, glutathione peroxidase and fibronectin in relation to abnormal umbilical artery velocimetry. Eur J Obstet Gynecol Reprod Biol 1998;80:39–44.
Miyauchi T, Masaki T. Pathophysiology of endothelin in the cardiovascular system. Annu Rev Physiol 1999;61:391–415.
Wilcox GR, Trudinger BJ, Cook CM, Wilcox WR, Connely AJ. Reduced fetal platelet counts in pregnancies with abnormal Doppler umbilical flow waveforms. Obstet Gynecol 1989;73: 639–43.
Ali MH, Schlidt SA, Chandel NS, Hynes KL, Schumacker PT, Gewertz BL. Endothelial permeability and IL-6 production during hypoxia: Role of ROS in signal transduction. Am J Physiol 1999;277:L1057–65.
Stallmach T, Hebisch G, Joller-Jemelka HI, Orban P, Schwaller J, Engelmann M. Cytokine production and visualized effects in the feto-maternal unit. Quantitative and topographic data on cytokines during intrauterine disease. Lab Invest 1995;73:384–92.
Thompson RS, Trudinger BJ, Cook CM, Giles WB. Umbilical artery velocity waveforms: Normal reference values for A/B ratio and Pourcelot ratio. Br J Obstet Gynaecol 1988;95:589–91.
Blick M, Sherwin SA, Rosenblum M, Gutterman J. Phase I study of recombinant tumor necrosis factor in cancer patients. Cancer Res 1987;47:2986–9.
Parsons PE, Moore FA, Moore EE, Ikle DN, Henson PM, Worthen GS. Studies on the role of tumor necrosis factor in adult respiratory distress syndrome. Am Rev Respir Dis 1992;146: 694–700.
Van Zee KJ, Kohno T, Fischer E, Rock CS, Moldawer LL, Lowry SF. Tumor necrosis factor soluble receptors circulate during experimental and clinical inflammation and can protect against excessive tumor necrosis factor alpha in vitro and in vivo. Proc Natl Acad Sci U S A 1992;89:4845–9.
Sterne G, Shields LE, Dubinsky TJ. Abnormal fetal cerebral and umbilical doppler measurements in fetuses with intrauterine growth restriction predict the severity of perinatal morbidity. J Clin Ultrasound 2001;29:146–51.
Jokic M, Guillois B, Cauquelin B, et al. Fetal distress increases interleukin-6 and interleukin-8 and decreases tumour necrosis factor-alpha cord blood levels in noninfected full-term neonates. Br J Obstet Gynaecol 2000;107:420–5.
Gomez R, Romero R, Ghezzi F, Yoon BH, Mazor M, Berry SM. The fetal inflammatory response syndrome. Am J Obstet Gynecol 1998;179:194–202.
Romero R, Gomez R, Ghezzi F, et al. A fetal systemic inflammatory response is followed by the spontaneous onset of preterm parturition. Am J Obstet Gynecol 1998;179:186–93.
Lockwood CJ. Recent advances in elucidating the pathogenesis of preterm delivery, the detection of patients at risk, and preventative therapies. Curr Opin Obstet Gynecol 1994;6:7–18.
Gohra H, Fujimura Y, Ito H, et al. Granulocyte elastase release and pulmonary hemodynamics in patients with atrial septal defect. Ann Thorac Surg 1998;65:719–23.
Kaplanski G, Teysseire N, Farnarier C, et al. IL-6 and IL-8 production from cultured human endothelial cells stimulated by infection with Rickettsia conorii via a cell-associated IL-1 alpha-dependent pathway. J Clin Invest 1995;96:2839–44.
Meng ZH, Dyer K, Billiar TR, Tweardy DJ. Essential role for IL-6 in postresuscitation inflammation in hemorrhagic shock. Am J Physiol Cell Physiol 2001;280:C343–51.
Misawa Y, Kawahito K, Konishi H, Fuse K. Cytokine mediated endothelial activation during and after normothermic cardiopulmonary bypass: Heparin-bonded versus non heparin-bonded circuits. ASAIO J 2000;46:740–3.
Kaifi JT, Diaconu E, Pearlman E. Distinct roles for PECAM-1, ICAM-1, and VCAM-1 in recruitment of neutrophils and eosinophils to the cornea in ocular onchocerciasis (river blindness). J Immunol 2001;166:6795–801.
Mukaida N. Interleukin-8: An expanding universe beyond neutrophil chemotaxis and activation. Int J Hematol 2000;72:391–8.
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Trudinger, B., Wang, J., Athayde, N. et al. Association of Umbilical Placental Vascular Disease With Fetal Acute Inflammatory Cytokine Responses. Reprod. Sci. 9, 152–157 (2002). https://doi.org/10.1177/107155760200900306
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DOI: https://doi.org/10.1177/107155760200900306