Persistency of high proinflammatory cytokine levels from colostrum to mature milk in preeclampsia Ays ¸e Binnur Erbag ˘cN a, * , Mustafa Baki C ¸ ekmen b ,O ¨ zcan Balat c , Ays ¸e Balat d , Fuat Aksoy c , Mehmet Tarakc ¸ Nog ˘lu a a Department of Biochemistry and Clinical Biochemistry, Faculty of Medicine, School of Medicine, University of Gaziantep, TR-27310, Gaziantep, Turkey b Department of Biochemistry and Clinical Biochemistry, School of Medicine, University of Kocaeli, Kocaeli, Turkey c Department of Obstetrics and Gynecology, School of Medicine, University of Gaziantep, Gaziantep, Turkey d Department of Pediatric Nephrology, School of Medicine, University of Gaziantep, Gaziantep, Turkey Received 11 January 2005; received in revised form 4 May 2005; accepted 17 May 2005 Available online 13 June 2005 Abstract Objectives: Recent evidence suggests a role of an excessive maternal inflammatory response in the pathogenesis of preeclampsia. Whether this imbalance can be transferred from mother to breast milk remains to be established. Design and methods: 15 preeclamptic and 15 healthy pregnant women were recruited in this study. Colostrum and milk samples were collected postpartum in the first 48 h and at 30 days, respectively. Samples were analyzed for interleukin (IL)-1h, IL-6, IL-8, tumor necrosis factor (TNF)-a and soluble IL-2R (sIL-2R) levels with chemiluminescence enzyme immunometric assays. Results: Colostrum cytokine levels corrected for gestational age and type of delivery were not significantly different in the two groups. Cytokine levels significantly decreased in mature milk versus colostrum in the control group (P < 0.05), but did not significantly decrease in the preeclampsia group (P > 0.05), except for TNF-a (P < 0.05). Mature milk IL-8 and TNF-a levels were higher in the preeclampsia group versus controls (P < 0.05). Conclusion: Results of this study show that proinflammatory cytokines in breast milk exhibit biological variation at different periods of human lactation. In preeclampsia, high cytokine levels persist at least for 30 days. These results suggest that preeclampsia may affect milk cytokine balance and offer an immunological signal for the host defense in high-risk neonates. D 2005 The Canadian Society of Clinical Chemists. All rights reserved. Keywords: Colostrum; Cytokine; Human milk; Preeclampsia; Soluble IL-2 receptor Introduction Preeclampsia is a highly variable and dangerous com- plication of the second half of pregnancy, labor or the early puerperium. The etiology of preeclampsia has previously been ascribed to generalized maternal endothelial dysfunc- tion [1], poor trophoblastic implantation [2,3] and excessive maternal inflammatory response [4]. Recent reports suggest that preeclampsia is associated with a Th1 predominant profile [5] and may be considered as a failure of the tolerance system allowing the second physiological tropho- blastic invasion [6]. It is known that Th1-type cytokines induce chronic inflammation. Th1-type immunity allows type 1 cytokines to initiate a cascade of immune-inflamma- tory processes in the maternal circulation, which includes activating macrophages to produce proinflammatory cyto- kines: interleukin (IL)-1h, IL-6, tumor necrosis factor-a (TNF-a) and IL-8 [5–7]. Recently, Redman et al. proposed an attractive hypoth- esis. Their hypothesis is that the intravascular excessive inflammatory response is not an epiphenomenon but is, in fact, the cause of the clinical syndrome of preeclampsia. They hypothesize that placental hypoxia, resulting from 0009-9120/$ - see front matter D 2005 The Canadian Society of Clinical Chemists. All rights reserved. doi:10.1016/j.clinbiochem.2005.05.004 * Corresponding author. Fax: +09 342/3601617. E-mail addresses: aerbagci@gantep.edu.tr, berbagci@hotmail.com (A.B. Erbag ˘cN). Clinical Biochemistry 38 (2005) 712 – 716