Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-6bf8c574d5-r8w4l Total loading time: 0 Render date: 2025-03-09T15:42:18.479Z Has data issue: false hasContentIssue false

7 - Immunological factors and placentation: implications for pre-eclampsia

from Part I - Basic science

Published online by Cambridge University Press:  03 September 2009

By
C. W. G. Redman  and
I. L. Sargent
Edited by
Fiona Lyall  and
Michael Belfort
Fiona Lyall
Affiliation:
University of Glasgow
Michael Belfort
Affiliation:
University of Utah
Get access

Summary

In this chapter what constitutes a systemic inflammatory response is described. Evidence is presented that normal pregnancy evokes such a response and that pre-eclampsia arises when the response becomes extreme and decompensates. The possible causes of systemic inflammation in pregnancy are reviewed, as is the relation between the inflammatory response and systemic oxidative stress. The interaction between systemic inflammation and changes in lipid and glucose metabolism are described and the relevance of long-term systemic inflammation as a predisposing risk factor is outlined. It is suggested that the metabolic results of systemic inflammation may endow a survival advantage for the fetus. Last, the systemic inflammation is related to other immune responses that are thought to be important for the success or failure of pregnancy.

Immune and inflammatory responses

In evolutionary terms, inflammatory responses are older than immune responses. The latter are superimposed on the former and cannot work without it. The primitive innate (inflammatory) system responds quickly and is relatively non-specific. The more sophisticated adaptive immune system is slow but precise, delivering antigen-specific responses with astonishing versatility and accuracy. The innate and adaptive systems are asymmetrically interdependent. The innate system does not need the adaptive system to function, whereas the adaptive system cannot function without signals from the innate system, nor need it provoke antibodies of antigen-specific cytotoxicity. This is a crucial consideration in relation to this chapter. A systemic inflammatory response is not necessarily generated by antigenic stimulation.

Type
Chapter
Information
Pre-eclampsia
Etiology and Clinical Practice
 , pp. 103 - 120
Publisher: Cambridge University Press
Print publication year: 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Ahmed, A., Dunk, C., Ahmad, S. and Khaliq, A. (2000). Regulation of placental vascular endothelial growth factor (VEGF) and placenta growth factor (PIGF) and soluble Flt-1 by oxygen – a review. Placenta, 21(Suppl. A), S16–24.CrossRefGoogle ScholarPubMed
Alexander, B. T., Cockrell, K. L., Massey, M. B., Bennett, W. A. and Granger, J. P. (2002). Tumor necrosis factor-alpha-induced hypertension in pregnant rats results in decreased renal neuronal nitric oxide synthase expression. Am. J. Hypertens., 15, 170–5.CrossRefGoogle ScholarPubMed
Arkwright, P. D., Rademacher, T. W., Dwek, R. A. and Redman, C. W. G. (1993). Pre-eclampsia is associated with an increase in trophoblast glycogen content and glycogen synthase activity, similar to that found in hydatidiform moles. J. Clin. Invest., 91, 2744–53.CrossRefGoogle ScholarPubMed
Arntzen, K. J., Liabakk, N. B., Jacobsen, G., Espevik, T. and Austgulen, R. (1995). Soluble tumor necrosis factor receptor in serum and urine throughout normal pregnancy and at delivery. Am. J. Reprod. Immunol., 34, 163–9.CrossRefGoogle ScholarPubMed
Aupeix, K., Hugel, B., Martin, T., et al. (1997). The significance of shed membrane particles during programmed cell death in vitro, and in vivo, in HIV-1 infection. J. Clin. Invest., 99, 1546–54.CrossRefGoogle ScholarPubMed
Austgulen, R., Lien, E., Liabakk, N. B., Jacobsen, G. and Arntzen, K. J. (1994). Increased levels of cytokines and cytokine activity modifiers in normal pregnancy. Eur. J. Obstet. Gynecol. Reprod. Biol., 57, 149–55.CrossRefGoogle ScholarPubMed
Barbour, L. A., Shao, J., Qiao, L., et al. (2002). Human placental growth hormone causes severe insulin resistance in transgenic mice. Am. J. Obstet. Gynecol., 186, 512–17.CrossRefGoogle ScholarPubMed
Barleon, B., Reusch, P., Totzke, F., et al. (2001). Soluble VEGFR-1 secreted by endothelial cells and monocytes is present in human serum and plasma from healthy donors. Angiogenesis, 4, 143–54.CrossRefGoogle ScholarPubMed
Barr, F. G., Biegel, J. A., Sellinger, B., Womer, R. B. and Emanuel, B. S. (1991). Molecular and cytogenetic analysis of chromosomal arms 2q and 13q in alveolar rhabdomyosarcoma. Genes Chromosomes Cancer, 3, 153–61.CrossRefGoogle ScholarPubMed
Barriga, C., Rodriguez, A. B. and Ortega, E. (1994). Increased phagocytic activity of polymorphonuclear leukocytes during pregnancy. Eur. J. Obstet. Gynecol. Reprod. Biol., 57, 43–6.CrossRefGoogle ScholarPubMed
Barton, J. R., Hiett, A. K., O'Connor, W. N., Nissen, S. E. and Greene, J.-W. J. (1991). Endomyocardial ultrastructural findings in preeclampsia. Am. J. Obstet. Gynecol., 165, 389–91.CrossRefGoogle ScholarPubMed
Bastard, J. P., Jardel, C., Bruckert, E., et al. (2000). Elevated levels of interleukin 6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss. J. Clin. Endocrinol. Metab., 85, 3338–42.Google ScholarPubMed
Belgore, F. M., Lip, G. Y. and Blann, A. D. (2000). Vascular endothelial growth factor and its receptor, Flt-1, in smokers and non-smokers. Br. J. Biomed. Sci., 57, 207–13.Google ScholarPubMed
Belgore, F. M., Blann, A. D., Li, S. H., Beevers, D. G. and Lip, G. Y. (2001). Plasma levels of vascular endothelial growth factor and its soluble receptor (SFlt-1) in essential hypertension. Am. J. Cardiol., 87, 805–7, A9.CrossRefGoogle Scholar
Benyo, D. F., Smarason, A., Redman, C. W. G., Sims, C. and Conrad, K. P. (2001). Expression of inflammatory cytokines in placentas from women with preeclampsia. J. Clin. Endocrinol. Metab., 86, 2505–12.Google ScholarPubMed
Beutler, B., Mahoney, J., Le-Trang, N., Pekala, P. and Cerami, A. (1985). Purification of cachectin, a lipoprotein lipase-suppressing hormone secreted by endotoxin-induced RAW 264.7 cells. J. Exp. Med., 161, 984–95.CrossRefGoogle ScholarPubMed
Blaschitz, A., Hutter, H. and Dohr, G. (2001). HLA Class I protein expression in the human placenta. Early Pregnancy, 5, 67–9.Google Scholar
Borzychowski, A. M., Croy, B. A., Chan, W. L., Redman, C. W. G. and Sargent, I. S. (2005). Changes in type 1 and type 2 immunity in normal pregnancy and pre-eclampsia may be mediated by NK cells. Eur. J. Immunol., 35, 3054–63.CrossRefGoogle Scholar
Boyd, P. A., Lindenbaum, R. H. and Redman, C. W. G. (1987). Pre-eclampsia and trisomy 13: a possible association. Lancet, ii, 425–7.CrossRefGoogle Scholar
Cester, N., Staffolani, R., Rabini, R. A., et al. (1994). Pregnancy induced hypertension, a role for peroxidation in microvillus plasma membranes. Mol. Cell. Biochem., 131, 151–5.CrossRefGoogle ScholarPubMed
Chaouat, G. (2003). Innately moving away from the Th1/Th2 paradigm in pregnancy. Clin. Exp. Immunol., 131, 393–5.CrossRefGoogle ScholarPubMed
Clark, D. E., Smith, S. K., He, Y., et al. (1998). A vascular endothelial growth factor antagonist is produced by the human placenta and released into the maternal circulation. Biol. Reprod., 59, 1540–8.CrossRefGoogle ScholarPubMed
Conrad, K. P., Miles, T. M. and Benyo, D. F. (1998). Circulating levels of immunoreactive cytokines in women with preeclampsia. Am. J. Reprod. Immunol., 40, 102–11.CrossRefGoogle ScholarPubMed
Crouch, S. P., Crocker, I. P. and Fletcher, J. (1995). The effect of pregnancy on polymorphonuclear leukocyte function. J. Immunol., 155, 5436–43.Google ScholarPubMed
Dalekos, G. N., Elisaf, M. S., Papagalanis, N., Tzallas, C. and Siamopoulos, K. C. (1996). Elevated interleukin-1 beta in the circulation of patients with essential hypertension before any drug therapy: a pilot study. Eur. J. Clin. Invest., 26, 936–9.CrossRefGoogle ScholarPubMed
Eiserich, J. P., Baldus, S., Brennan, M. L., et al. (2002). Myeloperoxidase, a leukocyte-derived vascular NO oxidase. Science, 296, 2391–4.CrossRefGoogle ScholarPubMed
Ellis, J., Wennerholm, U. B., Bengtsson, A., et al. (2001). Levels of dimethylarginines and cytokines in mild and severe preeclampsia. Acta Obstet. Gynecol. Scand., 80, 602–8.CrossRefGoogle ScholarPubMed
Esposito, K., Nappo, F., Marfella, R., et al. (2002). Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation, 106, 2067–72.CrossRefGoogle ScholarPubMed
Faas, M. M., Schuiling, G. A., Baller, J. F., Visscher, C. A. and Bakker, W. W. (1994). A new animal model for human preeclampsia: ultra-low-dose endotoxin infusion in pregnant rats. Am. J. Obstet. Gynecol., 171, 158–64.CrossRefGoogle ScholarPubMed
Felmeden, D. C., Spencer, C. G., Belgore, F. M., Blann, A. D., Beevers, D. G. and Lip, G. Y. (2003). Endothelial damage and angiogenesis in hypertensive patients: relationship to cardiovascular risk factors and risk factor management. Am. J. Hypertens., 16, 11–20.CrossRefGoogle ScholarPubMed
Gabay, C. and Kushner, I. (1999). Acute-phase proteins and other systemic responses to inflammation. N. Engl. J. Med., 340, 448–54.CrossRefGoogle ScholarPubMed
Gaber, L. W., Spargo, B. M. and Lindheimer, M. D. (1994). Renal pathology in pre-eclampsia. Bailliere's Clin. Obstet. Gynaecol., 8, 443–68.CrossRefGoogle ScholarPubMed
Gallucci, S. and Matzinger, P. (2001). Danger signals: SOS to the immune system. Curr. Opin. Immunol., 13, 114–19.CrossRefGoogle ScholarPubMed
Garner, P. R., D'Alton, M. E., Dudley, D. K., Huard, P. and Hardie, M. (1990). Preeclampsia in diabetic pregnancies. Am. J. Obstet. Gynecol., 163, 505–8.CrossRefGoogle ScholarPubMed
Gatti, L., Tenconi, P. M., Guarneri, D., et al. (1994). Hemostatic parameters and platelet activation by flow-cytometry in normal pregnancy: a longitudinal study. Int. J. Clin. Lab. Res., 24, 217–19.CrossRefGoogle ScholarPubMed
Gratacos, E., Casals, E., Deulofeu, R., Cararach, V., Alonso, P. L. and Fortuny, A. (1998). Lipid peroxide and vitamin E patterns in pregnant women with different types of hypertension in pregnancy. Am. J. Obstet. Gynecol., 178, 1072–6.CrossRefGoogle ScholarPubMed
Greer, I. A., Haddad, N. G., Dawes, J., Johnstone, F. D. and Calder, A. A. (1989). Neutrophil activation in pregnancy-induced hypertension. Br. J. Obstet. Gynaecol., 96, 978–82.CrossRefGoogle ScholarPubMed
Greer, I. A., Lyall, F., Perera, T., Boswell, F. and Macara, L. M. (1994). Increased concentrations of cytokines interleukin-6 and interleukin-1 receptor antagonist in plasma of women with preeclampsia: a mechanism for endothelial dysfunction?Obstet. Gynecol., 84, 937–40.Google ScholarPubMed
Haddad, J. J. (2002). Antioxidant and prooxidant mechanisms in the regulation of redox(y)-sensitive transcription factors. Cell Signal, 14, 879–97.CrossRefGoogle Scholar
Haeger, M., Bengtson, A., Karlsson, K. and Heideman, M. (1989). Complement activation and anaphylatoxin (C3a and C5a) formation in preeclampsia and by amniotic fluid. Obstet. Gynecol., 73, 551–6.Google ScholarPubMed
Haig, D. (1993). Genetic conflicts in human pregnancy. Q. Rev. Biol., 68, 495–532.CrossRefGoogle ScholarPubMed
Halligan, A., Bonnar, J., Sheppard, B., Darling, M. and Walshe, J. (1994). Haemostatic, fibrinolytic and endothelial variables in normal pregnancies and pre-eclampsia. Br. J. Obstet. Gynaecol., 101, 488–92.CrossRefGoogle ScholarPubMed
Hansson, G. K., Libby, P., Schönbeck, U. and Yan, Z. Q. (2002). Innate and adaptive immunity in the pathogenesis of atherosclerosis. Circ. Res., 91, 281–91.CrossRefGoogle ScholarPubMed
Harris, H. W., Gosnell, J. E. and Kumwenda, Z. L. (2001). The lipemia of sepsis: triglyceride-rich lipoproteins as agents of innate immunity. J. Endotoxin Res., 6, 421–30.Google Scholar
Hayakawa, M., Miyashita, H., Sakamoto, I., et al. (2003). Evidence that reactive oxygen species do not mediate NF-kappaB activation. EMBO J., 22, 3356–66.CrossRefGoogle Scholar
Hensley, K., Robinson, K. A., Gabbita, S. P., Salsman, S. and Floyd, R. A. (2000). Reactive oxygen species, cell signaling, and cell injury. Free Rad. Biol. Med., 28, 1456–62.CrossRefGoogle ScholarPubMed
Hirosumi, J., Tuncman, G., Chang, L., et al. (2002). A central role for JNK in obesity and insulin resistance. Nature, 420, 333–6.CrossRefGoogle ScholarPubMed
Holland, E. (1909). Recent work on the aetiology of eclampsia. J. Obstet. Gynaecol. Br. Emp., 16, 255–73.CrossRefGoogle Scholar
Hornnes, P. J. (1985). On the decrease of glucose tolerance in pregnancy. A review. Diabet. Metab., 11, 310–15.Google ScholarPubMed
Hubel, C. A. (1998). Dyslipidemia, iron, and oxidative stress in preeclampsia, assessment of maternal and feto-placental interactions. Semin. Reprod. Endocrinol., 16, 75–92.CrossRefGoogle ScholarPubMed
Hubel, C. A., McLaughlin, M. K., Evans, R. W., Hauth, B. A., Sims, C. J. and Roberts, J. M. (1996). Fasting serum triglycerides, free fatty acids, and malondialdehyde are increased in preeclampsia, are positively correlated, and decrease within 48 hours post partum. Am. J. Obstet. Gynecol., 174, 975–82.CrossRefGoogle ScholarPubMed
Huppertz, B., Frank, H. G., Kingdom, J. C., Reister, F. and Kaufmann, P. (1998). Villous cytotrophoblast regulation of the syncytial apoptotic cascade in the human placenta. Histochem. Cell Biol., 110, 495–508.CrossRefGoogle ScholarPubMed
Impey, L., Greenwood, C., Sheil, O., MacQuillan, K., Reynolds, M. and Redman, C. (2001). The relation between pre-eclampsia at term and neonatal encephalopathy. Arch. Dis. Child. Fetal Neonatal Ed., 85, F170–2.CrossRefGoogle ScholarPubMed
Ishihara, N., Matsuo, H., Murakoshi, H., Laoag-Fernandez, J. B., Samoto, T. and Maruo, T. (2002). Increased apoptosis in the syncytiotrophoblast in human term placentas complicated by either preeclampsia or intrauterine growth retardation. Am. J. Obstet. Gynecol., 186, 158–66.CrossRefGoogle ScholarPubMed
Isomaa, B. (2003). A major health hazard: the metabolic syndrome. Life Sci., 73, 2395–411.CrossRefGoogle Scholar
Johansen, K. A., Williams, J. H. and Stark, J. M. (1981). Acute-phase C56-forming ability and concentrations of complement components in normotensive and hypertensive pregnancies. Br. J. Obstet. Gynaecol., 88, 504–12.CrossRefGoogle ScholarPubMed
Johansen, M., Redman, C. W. G., Wilkins, T. and Sargent, I. L. (1999). Trophoblast deportation in human pregnancy – its relevance for pre-eclampsia. Placenta, 20, 531–9.CrossRefGoogle ScholarPubMed
Jones, C. J. and Fox, H. (1980). An ultrastructural and ultrahistochemical study of the human placenta in maternal pre-eclampsia. Placenta, 1, 61–76.CrossRefGoogle ScholarPubMed
Kaaja, R., Laivuori, H., Laakso, M., Tikkanen, M. J. and Ylikorkala, O. (1999). Evidence of a state of increased insulin resistance in preeclampsia. Metabolism, 48, 892–6.CrossRefGoogle ScholarPubMed
Kabbinavar, F., Hurwitz, H. I., Fehrenbacher, L., et al. (2003). Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J. Clin. Oncol., 21, 60–5.CrossRefGoogle ScholarPubMed
Kendall, R. L., Wang, G. and Thomas, K. A. (1996). Identification of a natural soluble form of the vascular endothelial growth factor receptor, FLT-1, and its heterodimerization with KDR. Biochem. Biophys. Res. Commun., 226, 324–8.CrossRefGoogle ScholarPubMed
Knight, M., Redman, C. W., Linton, E. A. and Sargent, I. L. (1998). Shedding of syncytiotrophoblast microvilli into the maternal circulation in pre-eclamptic pregnancies. Br. J. Obstet. Gynaecol., 105, 632–40.CrossRefGoogle ScholarPubMed
Konijnenberg, A., Stokkers, E. W., Post, J., et al. (1997). Extensive platelet activation in preeclampsia compared with normal pregnancy, enhanced expression of cell adhesion molecules. Am. J. Obstet. Gynecol., 176, 461–9.CrossRefGoogle ScholarPubMed
Kupferminc, M. J., Peaceman, A. M., Wigton, T. R., Rehnberg, K. A. and Socol, M. L. (1994). Tumor necrosis factor-alpha is elevated in plasma and amniotic fluid of patients with severe preeclampsia. Am. J. Obstet. Gynecol., 170, 1752–7.CrossRefGoogle ScholarPubMed
Lechleitner, M., Koch, T., Herold, M., Dzien, A. and Hoppichler, F. (2000). Tumour necrosis factor-alpha plasma level in patients with type 1 diabetes mellitus and its association with glycaemic control and cardiovascular risk factors. J. Intern. Med., 248, 67–76.CrossRefGoogle ScholarPubMed
Levy, R., Smith, S. D., Chandler, K., Sadovsky, Y. and Nelson, D. M. (2000). Apoptosis in human cultured trophoblasts is enhanced by hypoxia and diminished by epidermal growth factor. Am. J. Physiol. Cell Physiol., 278, C982–8.CrossRefGoogle ScholarPubMed
Li, D. K. and Wi, S. (2000). Changing paternity and the risk of preeclampsia/eclampsia in the subsequent pregnancy. Am. J. Epidemiol., 151, 57–62.CrossRefGoogle ScholarPubMed
Li, N. and Karin, M. (1999). Is NF-kappaB the sensor of oxidative stress?FASEB J., 13, 1137–43.CrossRefGoogle ScholarPubMed
Lie, R. T., Rasmussen, S., Brunborg, H., Gjessing, H. K., Lie, N. E. and Irgens, L. M. F. (1998). Fetal and maternal contributions to risk of pre-eclampsia: population based study. Br. Med. J., 316, 1343–7.CrossRefGoogle ScholarPubMed
Lo, Y. M., Leung, T. N., Tein, M. S., et al. (1999). Quantitative abnormalities of fetal DNA in maternal serum in preeclampsia. Clin. Chem., 45, 184–8.Google ScholarPubMed
Lorentzen, B., Drevon, C. A., Endresen, M. J. and Henriksen, T. (1995). Fatty acid pattern of esterified and free fatty acids in sera of women with normal and pre-eclamptic pregnancy. Br. J. Obstet. Gynaecol., 102, 530–7.CrossRefGoogle ScholarPubMed
Luft, F. C. (2002). Proinflammatory effects of angiotensin II and endothelin: targets for progression of cardiovascular and renal diseases. Curr. Opin. Nephrol. Hypertens., 11, 59–66.CrossRefGoogle ScholarPubMed
McCracken, S. A., Gallery, E. D. M. and Morris, J. M. (2004). Pregnancy-specific down regulation of NF-kappaB expression in T cells is essential for the maintenance of cytokine profile required for pregnancy success. J. Immunol., 172, 4583–91.CrossRefGoogle Scholar
Mantzoros, C. S., Moschos, S., Avramopoulos, I., et al. (1997). Leptin concentrations in relation to body mass index and the tumor necrosis factor-alpha system in humans. J. Clin. Endocrinol. Metab., 82, 3408–13.Google ScholarPubMed
Martin, U., Davies, C., Hayavi, S., Hartland, A. and Dunne, F. (1999). Is normal pregnancy atherogenic?Clin. Sci. Colch., 96, 421–5.CrossRefGoogle ScholarPubMed
Marzi, M., Vigano, A., Trabattoni, D., et al. (1996). Characterization of type 1 and type 2 cytokine production profile in physiologic and pathologic human pregnancy. Clin. Exp. Immunol., 106, 127–33.CrossRefGoogle ScholarPubMed
Matzinger, P. (2002). The danger model: a renewed sense of self. Science, 296, 301–5.CrossRefGoogle ScholarPubMed
Maynard, S. E., Min, J. Y., Merchan, J., et al. (2003). Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J. Clin. Invest., 111, 649–58.CrossRefGoogle ScholarPubMed
Melczer, Z., Banhidy, F., Csomor, S., et al. (2003). Influence of leptin and the TNF system on insulin resistance in pregnancy and their effect on anthropometric parameters of newborns. Acta Obstet. Gynecol. Scand., 82, 432–8.CrossRefGoogle ScholarPubMed
Mellembakken, J. R., Aukrust, P., Olafsen, M. K., Ueland, T., Hestdal, K. and Videm, V. (2002). Activation of leukocytes during the uteroplacental passage in preeclampsia. Hypertension, 39, 155–60.CrossRefGoogle ScholarPubMed
Morris, J. M., Gopaul, N. K., Endresen, M. J., et al. (1998). Circulating markers of oxidative stress are raised in normal pregnancy and pre-eclampsia. Br. J. Obstet. Gynaecol., 105, 1195–9.CrossRefGoogle ScholarPubMed
Nelson, D. M. (1996). Apoptotic changes occur in syncytiotrophoblast of human placental villi where fibrin type fibrinoid is deposited at discontinuities in the villous trophoblast. Placenta, 17, 387–91.CrossRefGoogle ScholarPubMed
Ness, R. B. and Roberts, J. M. (1996). Heterogeneous causes constituting the single syndrome of preeclampsia: a hypothesis and its implications. Am. J. Obstet. Gynecol., 175, 1365–70.CrossRefGoogle ScholarPubMed
Nisell, H., Erikssen, C., Persson, B. and Carlstrom, K. (1999). Is carbohydrate metabolism altered among women who have undergone a preeclamptic pregnancy?Gynecol. Obstet. Invest., 48, 241–6.CrossRefGoogle ScholarPubMed
Pepys, M. B. and Hirschfield, G. M. (2003). C-reactive protein: a critical update. J. Clin. Invest., 112, 299.CrossRefGoogle Scholar
Perry, K. G. J. and Martin, J. N. J. (1992). Abnormal hemostasis and coagulopathy in preeclampsia and eclampsia. Clin. Obstet. Gynecol., 35, 338–50.CrossRefGoogle ScholarPubMed
Pickup, J. C., Chusney, G. D., Thomas, S. M. and Burt, D. (2000). Plasma interleukin-6, tumour necrosis factor alpha and blood cytokine production in type 2 diabetes. Life Sci., 67, 291–300.CrossRefGoogle ScholarPubMed
Pitkin, R. M. and Witte, D. L. (1979). Platelet and leukocyte counts in pregnancy. J. Am. Med. Ass., 242, 2696–8.CrossRefGoogle ScholarPubMed
Rebelo, I., Carvalho Guerra, F., Pereira Leite, L. and Quintanilha, A. (1995). Lactoferrin as a sensitive blood marker of neutrophil activation in normal pregnancies. Eur. J. Obstet. Gynecol. Reprod. Biol., 62, 189–94.CrossRefGoogle ScholarPubMed
Redman, C. W. G. (1991). Current topic. Pre-eclampsia and the placenta. Placenta, 12, 301–8.CrossRefGoogle ScholarPubMed
Redman, C. W. G. (1992). The placenta and pre-eclampsia. In The Human Placenta, ed. Redman, C. W. G., Sargent, I. L. and Starkey, P. M.. Oxford: Blackwell Scientific Publications, pp. 433–67.Google Scholar
Redman, C. W. G. and Sargent, I. L. (2000). Placental debris, oxidative stress and pre-eclampsia. Placenta, 21, 597–602.CrossRefGoogle ScholarPubMed
Redman, C. W. G., Sacks, G. P., and Sargent, I. L. (1999). Preeclampsia, an excessive maternal inflammatory response to pregnancy. Am. J. Obstet. Gynecol., 180, 499–506.CrossRefGoogle Scholar
Rein, D. T., Schondorf, T., Gohring, U. J., et al. (2002). Cytokine expression in peripheral blood lymphocytes indicates a switch to T(HELPER) cells in patients with preeclampsia. J. Reprod. Immunol., 54, 133–42.CrossRefGoogle Scholar
Ridker, P. M. (2001). High-sensitivity C-reactive protein: potential adjunct for global risk assessment in the primary prevention of cardiovascular disease. Circulation, 103, 1813–18.CrossRefGoogle ScholarPubMed
Roberts, J. M., Taylor, R. N., Musci, T. J., Rodgers, G. M., Hubel, C. A. and McLaughlin, M. K. (1989). Preeclampsia, an endothelial cell disorder. Am. J. Obstet. Gynecol., 161, 1200–4.CrossRefGoogle ScholarPubMed
Roberts, R. N., Henriksen, J. E. and Hadden, D. R. (1998). Insulin sensitivity in pre-eclampsia. Br. J. Obstet. Gynaecol., 105, 1095–100.CrossRefGoogle ScholarPubMed
Rock, F. L., Hardiman, G., Timans, J. C., Kastelein, R. A. and Bazan, J. F. (1998). A family of human receptors structurally related to Drosophila Toll. Proc. Natl Acad. Sci. USA, 95, 588–93.CrossRefGoogle ScholarPubMed
Ros, H. S., Cnattingius, S. and Lipworth, L. (1998). Comparison of risk factors for preeclampsia and gestational hypertension in a population-based cohort study. Am. J. Epidemiol., 147, 1062–70.CrossRefGoogle Scholar
Sacks, G. P., Studena, K., Sargent, I. L. and Redman, C. W. G. (1998). Normal pregnancy and preeclampsia both produce inflammatory changes in peripheral blood leukocytes akin to those of sepsis. Am. J. Obstet. Gynecol., 179, 80–6.CrossRefGoogle ScholarPubMed
Sacks, G. P., Sargent, I. L. and Redman, C. W. G. (1999). An innate view of human pregnancy. Immunol. Today, 20, 114–18.CrossRefGoogle ScholarPubMed
Sacks, G. P., Redman, C. W. G. and Sargent, I. L. (2003). Monocytes are primed to express the Th1 type cytokine IL-12 in normal human pregnancy: an intracellular flow cytometric analysis of peripheral blood mononuclear cells. Clin. Exp. Immunol., 131, 490–7.CrossRefGoogle Scholar
Sacks, G. P., Seyani, L., Lavery, S. and Trew, G. (2004). Maternal C-reactive protein levels are raised at 4 weeks gestationHum. Reprod., 19, 1025–30.CrossRefGoogle ScholarPubMed
Saito, S., Sakai, M., Sasaki, Y., Tanebe, K., Tsuda, H. and Michimata, T. (1999). Quantitative analysis of peripheral blood Th0, Th1, Th2 and the Th1:Th2 cell ratio during normal human pregnancy and preeclampsia. Clin. Exp. Immunol., 117, 550–5.CrossRefGoogle ScholarPubMed
Sakai, M., Tsuda, H., Tanebe, K., Sasaki, Y. and Saito, S. (2002). Interleukin-12 secretion by peripheral blood mononuclear cells is decreased in normal pregnant subjects and increased in preeclamptic patients. Am. J. Reprod. Immunol., 47, 91–7.CrossRefGoogle ScholarPubMed
Schena, F. P., Manno, C., Selvaggi, L., Loverro, G., Bettocchi, S. and Bonomo, L. (1982). Behaviour of immune complexes and the complement system in normal pregnancy and pre-eclampsia. J. Clin. Lab. Immunol., 7, 21–6.Google ScholarPubMed
Schrocksnadel, H., Daxenbichler, G., Artner, E., Steckel Berger, G. and Dapunt, O. (1993). Tumor markers in hypertensive disorders of pregnancy. Gynecol. Invest., 35, 204–8.CrossRefGoogle ScholarPubMed
Sethi, J. K. and Hotamisligil, G. S. (1999). The role of TNF alpha in adipocyte metabolism. Semin. Cell. Dev. Biol., 10, 19–29.CrossRefGoogle ScholarPubMed
Shanklin, D. R. and Sibai, B. M. (1989). Ultrastructural aspects of preeclampsia. I. Placental bed and uterine boundary vessels. Am. J. Obstet. Gynecol., 161, 735–41.CrossRefGoogle ScholarPubMed
Shibuya, T., Izuchi, K., Kuroiwa, A., Okabe, N. and Shirakawa, K. (1987). Study on nonspecific immunity in pregnant women: increased chemiluminescence response of peripheral blood phagocytes. Am. J. Reprod. Immunol. Microbiol., 15, 19–23.CrossRefGoogle ScholarPubMed
Sibai, B. M., Gordon, T., Thom, E., et al. (1995). Risk factors for preeclampsia in healthy nulliparous women: a prospective multicenter study. The National Institute of Child Health and Human Development Network of Maternal–Fetal Medicine Units. Am. J. Obstet. Gynecol., 172, 642–8.CrossRefGoogle ScholarPubMed
Smarason, A. K., Gunnarsson, A., Alfredsson, J. H. and Valdimarsson, H. (1986). Monocytosis and monocytic infiltration of decidua in early pregnancy. J. Clin. Lab. Immunol., 21, 1–5.Google ScholarPubMed
Smarason, A. K., Sargent, I. L., Starkey, P. M. and Redman, C. W. G. (1993). The effect of placental syncytiotrophoblast microvillous membranes from normal and pre-eclamptic women on the growth of endothelial cells in vitro. Br. J. Obstet. Gynaecol., 100, 943–9.CrossRefGoogle ScholarPubMed
Stallmach, T., Hebisch, G., Joller, H., Kolditz, P. and Engelmann, M. (1995). Expression pattern of cytokines in the different compartments of the feto-maternal unit under various conditions. Reprod. Fertil. Dev., 7, 1573–80.CrossRefGoogle ScholarPubMed
Stanley, K., Fraser, R. and Bruce, C. (1998). Physiological changes in insulin resistance in human pregnancy: longitudinal study with the hyperinsulinaemic euglycaemic clamp technique. Br. J. Obstet. Gynaecol., 105, 756–9.CrossRefGoogle ScholarPubMed
Strevens, H., Wide-Swensson, D., Hansen, A., et al. (2003). Glomerular endotheliosis in normal and pregnancy and pre-eclampsia. Br. J. Obstet. Gynaecol., 110, 831–6.CrossRefGoogle ScholarPubMed
Taylor, R. N., Crombleholme, W. R., Friedman, S. A., Jones, L. A., Casal, D. C. and Roberts, J. M. (1991). High plasma cellular fibronectin levels correlate with biochemical and clinical features of preeclampsia but cannot be attributed to hypertension alone. Am. J. Obstet. Gynecol., 165, 895–901.CrossRefGoogle ScholarPubMed
Tedder, R. S., Nelson, M. and Eisen, V. (1975). Effects on serum complement of normal and pre-eclamptic pregnancy and of oral contraceptives. Br. J. Exp. Pathol., 56, 389–95.Google ScholarPubMed
Teran, E., Escudero, C., Moya, W., Flores, M., Vallance, P. and Lopez-Jaramillo, P. (2001). Elevated C-reactive protein and pro-inflammatory cytokines in Andean women with pre-eclampsia. Int. J. Gynaecol. Obstet., 75, 243–9.CrossRefGoogle ScholarPubMed
Terrone, D. A., Rinehart, B. K., May, W. L., Moore, A, Magann, E. F. and Martin, J. N. (2000). Leukocytosis is proportional to HELLP syndrome severity: evidence for an inflammatory form of preeclampsia. South Med. J., 93, 768–71.CrossRefGoogle ScholarPubMed
Ukkola, O. and Bouchard, C. (2001). Clustering of metabolic abnormalities in obese individuals: the role of genetic factors. Ann. Med., 33, 79–90.CrossRefGoogle ScholarPubMed
Vince, G. S., Starkey, P. M., Austgulen, D. and Redman, C. W. (1995). Interleukin-6, tumour necrosis factor and soluble tumour necrosis factor receptors in women with pre-eclampsia. Br. J. Obstet. Gynaecol., 102, 20–5.CrossRefGoogle ScholarPubMed
Vitoratos, N., Salamalekis, E., Dalamaga, N., Kassanos, D. and Creatsas, G. (1999). Defective antioxidant mechanisms via changes in serum ceruloplasmin and total iron binding capacity of serum in women with pre-eclampsia. Eur. J. Obstet. Gynecol. Reprod. Biol., 84, 63–7.CrossRefGoogle ScholarPubMed
Dadelszen, P., Hurst, G. and Redman, C. W. G. (1999). The supernatants from co-cultured endothelial cells and syncytiotrophoblast microvillous membranes activate peripheral blood leukocytes in vitro. Hum. Reprod., 14, 919–24.CrossRefGoogle Scholar
Wegmann, T. G., Lin, H., Guilbert, L. and Mosmann, T. R. (1993). Bidirectional cytokine interactions in the maternal–fetal relationship: is successful pregnancy a Th2 phenomenon?Immunol. Today, 14, 353–6.CrossRefGoogle ScholarPubMed
Wickens, D., Wilkins, M. H., Lunec, J., Ball, G. and Dormandy, T. L. (1981). Free radical oxidation (peroxidation) products in plasma in normal and abnormal pregnancy. Ann. Clin. Biochem., 18, 158–62.CrossRefGoogle ScholarPubMed
Willis, C., Morris, J. M., Danis, V. and Gallery, E. D. (2003). Cytokine production by peripheral blood monocytes during the normal human ovulatory menstrual cycle. Hum. Reprod., 18, 1173–8.CrossRefGoogle ScholarPubMed
Yang, J. C., Haworth, L., Sherry, R. M., et al. (2003). A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N. Engl. J. Med., 349, 427–34.CrossRefGoogle ScholarPubMed
Yoo, J. Y. and Desiderio, S. (2003). Innate and acquired immunity intersect in a global view of the acute-phase response. Proc. Natl Acad. Sci. USA, 100, 1157–62.CrossRefGoogle Scholar
Yudkin, J. S., Stehouwer, C. D., Emeis, J. J. and Coppack, S. W. (1999). C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue?Arterioscler. Thromb. Vasc. Biol., 19, 972–8.CrossRefGoogle ScholarPubMed
Yura, S., Sagawa, N., Itoh, H., et al. (2003). Resistin is expressed in the human placenta. J. Clin. Endocrinol. Metab., 88, 1394–7.CrossRefGoogle ScholarPubMed
Zabriskie, J. R. (1963). Effect of cigarette smoking during pregnancy. Study of 2000 cases. Obstet. Gynecol., 21, 405–11.Google Scholar
Zarkesh-Esfahani, H., Pockley, G., Metcalfe, R. A., et al. (2001). High-dose leptin activates human leukocytes via receptor expression on monocytes. J. Immunol., 167, 4593–9.CrossRefGoogle ScholarPubMed
Ziccardi, P., Nappo, F., Giugliano, G., et al. (2002). Reduction of inflammatory cytokine concentrations and improvement of endothelial functions in obese women after weight loss over one year. Circulation, 105, 804–9.CrossRefGoogle ScholarPubMed
Zimmerman, G. A., Prescott, S. M. and McIntyre, T. M. (1992). Endothelial cell interactions with granulocytes: tethering and signaling molecules. Immunol. Today, 13, 93–100.CrossRefGoogle ScholarPubMed
Zusterzeel, P. L., Mulder, T. P., Peters, W. H., Wiseman, S. A. and Steegers, E. A. (2000). Plasma protein carbonyls in nonpregnant, healthy pregnant and preeclamptic women. Free Rad. Res., 33, 471–6.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×