Published Online
on September 27, 2004

A more recent version of this article appeared on November 1, 2004

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Submitted on May 14, 2004
Revised on June 8, 2004

Short- and Long-Term Changes in Plasma Inflammatory Markers Associated With Preeclampsia

Dilys J. Freeman^*; Frances McManus; Elizabeth Ann Brown; Lynne Cherry; John Norrie; Jane E. Ramsay; Peter Clark; Isobel D. Walker; Naveed Sattar; and Ian A. Greer

From the Division of Developmental Medicine (D.J.F., F.M., E.A.B., J.E.R., N.S., I.A.G.) and Department of Pathological Biochemistry (L.C., N.S.), University of Glasgow; Centre for Healthcare Randomised Trials (J.N.), Health Services Research Unit, Aberdeen University; Department of Transfusion Medicine (P.C.), Ninewells Hospital, Dundee; and Department of Haematology (I.D.W.), Royal Infirmary, Glasgow, United Kingdom.

^* To whom correspondence should be addressed. E-mail: d.freeman{at}clinmed.gla.ac.uk.

Abstract--Preeclampsia is characterized by hypertension, dyslipidemia, and increased systemic inflammatory response and has been associated with an increased maternal risk of cardiovascular disease later in life. Low-grade chronic inflammation is a risk factor for cardiovascular disease. This study examined changes in inflammatory markers prospectively during pregnancy, the current inflammatory status of women who had a pregnancy complicated by preeclampsia 20 years previously against matched controls, and the association between inflammatory genes and risk of preeclampsia in a case (n=106) control (n=212) study. In control pregnancies (n=34), mean interleukin-10 (IL-10) levels increased 38% (P=0.012) and tumor necrosis factor- (TNF-) by 33% (P=0.024) between the first and third trimesters. The mean preeclampsia group IL-10 and TNF- rose by 43% (P=0.013 and P=0.0065, respectively) from the first to the third trimester. In women with preeclampsia only, plasma IL-6 increased from the first to the third trimester (1.66 [2.04] to 2.94 [2.47] pg/mL; P=0.0004). Twenty years after the index pregnancy, women who had had preeclampsia demonstrated significantly higher IL-6 to IL-10 ratio (3.96 [6.07] versus 2.12 [1.89]; P=0.034) compared with a healthy index pregnancy 20 years previously, that persisted after adjustment for smoking and current body mass index. The IL-1 (C-511T), IL-6 (G-174C), TNF- (G-308A), E-selectin (S128R), intercellular adhesion molecule-1 (K469E), and C-reactive protein (C1059G) polymorphisms were not associated with risk of developing preeclampsia. In conclusion, preeclampsia is associated with short- and long-term changes in inflammatory status.

Key words: preeclampsia • polymorphism • cardiovascular diseases • inflammation

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