Fetal and Pediatric Pathology, 33:196–197, 2014 C Informa Healthcare USA, Inc. Copyright  ISSN: 1551-3815 print / 1551-3823 online DOI: 10.3109/15513815.2014.898722

LETTER TO THE EDITOR

Fetal Pediatr Pathol Downloaded from informahealthcare.com by Yale Dermatologic Surgery on 09/30/14 For personal use only.

The Evaluation of Inflammatory Markers in Umbilical Cord Blood Ibrahim Aydin,1 Fevzi Nuri Aydin,2 and Mehmet Agilli3 1

Department of Biochemistry, Sarikamis Military Hospital, Kars, Turkey; 2 Department of Biochemistry, Sirnak Military Hospital, Sirnak, Turkey; 3 Department of Biochemistry, Agri Military Hospital, Agri, Turkey

We have read with great interest the article by Lausten-Thomsen et al. entitled “Inflammatory Markers in Umbilical Cord Blood from Small-For-Gestational-Age Newborns” in which they report Interleukin 6 (IL-6), Tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) levels in umbilical cord blood from small-for-gestational-age (SGA) and healthy newborns. In this regard, we would like to make some additions to paper in respect to interpretations of biochemical markers. Normal CRP concentration in healthy human serum is usually lower than 10 mg/L, slightly increasing with aging. Acute inflammatory response causes release of IL-6 and other cytokines that trigger the synthesis of CRP by the liver. In this article, IL-6 levels reported as elevated but CRP levels have remained in normal range. In this situation, increasing in IL-6 levels should be approached suspiciously. Although decreased TNF-α level was compatible with IL-6 levels, increased IL-6 levels did not cause CRP elevation in this study. Keywords: C-reactive protein, inflammation, interleukine-6

We have read with great interest the article by Lausten-Thomsen et al. [1] entitled “Inflammatory Markers in Umbilical Cord Blood from Small-For-Gestational-Age Newborns” in which they report Interleukin 6 (IL-6), Tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) levels in umbilical cord blood from small-for-gestationalage (SGA) and healthy newborns. In their paper, authors report some inflammatory markers’ levels in umbilical cord blood and speculate that anti-inflammatory therapies in the future could be used in order to treat and/or prevent some of the inflammation-associated morbidities in neonates suffering from intrauterine growth restriction (IUGR). In this regard, we would like to make some additions to paper in respect to interpretations of biochemical markers. CRP is used mainly as a marker of inflammation. Normal CRP concentration in healthy human serum is usually lower than 10 mg/L, slightly increasing with aging. Acute inflammatory response causes release of IL-6 and other cytokines that trigger the synthesis of CRP by the liver. In this article, IL-6 levels reported as elevated but CRP levels have remained in normal range. In this situation, increasing in IL-6 levels should be approached suspiciously. IL-6 is secreted by macrophages and T-cells to stimulate immune response. In addition, smooth muscle cells also produce IL-6. IL-6 is an interleukin that acts as both a pro-inflammatory and an anti-inflammatory cytokine [2]. IL-6’s role as an Received 19 February 2014; accepted 24 February 2014. Address correspondence to Dr Ibrahim Aydin, Department of Biochemistry, Sarikamis Military Hospital, Kars, Turkey. E-mail: [email protected]

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Fetal Pediatr Pathol Downloaded from informahealthcare.com by Yale Dermatologic Surgery on 09/30/14 For personal use only.

Letter to the Editor

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anti-inflammatory cytokine is through its inhibitory effects on TNF-α and IL-1. Although decreased TNF-α level was compatible with IL-6 levels, increased IL-6 levels did not cause CRP elevation in this study. IL-6 is significantly elevated both in inflammation and vigorous exercise. Because of intense muscular contractions during delivery, we suggest that delivery mode (Vaginal or Cesarean Section) and delivery time should be determined for this study. Furthermore, measuring IL-6 levels in maternal blood after delivery provides more accurate information about the source of IL-6. Otherwise, measuring neopterin levels, a useful inflammatory marker, in cord blood may reflect macrophage activation [3]. SGA babies are those who are smaller in size than normal for the gestational age. The term SGA used is associated with IUGR. However, not all fetuses with SGA are pathologically growth restricted and, in fact, may be constitutionally small. In order to eliminate confusion on this issue, we thought that excluding the babies whose mothers are shorter than normal would be useful in this study. Normal fetal growth is modified by maternal, fetal, placental and environmental factors [4]. Maternal factors such as infections, chronic inflammatory illnesses and the other inflammatory processes can influence intrauterine growth of fetus and cause IUGR [5]. On the other hand, in order to obtain relatively homogenous groups of infants, authors had excluded children who were exposed to maternal chronic disease and gestational diabetes. However, to eliminate maternal factors, inflammatory markers including IL-6, TNF-α and CRP should be studied both maternal and cord sera. Declaration of Interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. REFERENCES [1] Lausten-Thomsen U, Olsen M, Greisen G, Schmiegelow K. Inflammatory markers in umbilical cord blood from small-for-gestational-age newborns. Fetal Pediatr Pathol. 2014;33(2):114–118. [Epub ahead of print]. [2] Petersen AM, Pedersen BK. The anti-inflammatory effect of exercise. J ApplPhysiol (1985) 2005; 98:1154–1162. [3] Cayci T, Akgul EO, Kurt YG, et al. Cord blood and maternal serum neopterin concentrations in patients with pre-eclampsia. ClinChem Lab Med 2010;48:1127–1131. [4] Murthi P, Kalionis B, Rajaraman G, et al. The role of homeobox genes in the development of placental insufficiency. Fetal Diagn Ther 2012;32:225–230. [5] Pereira L, Petitt M, Fong A, et al. Intrauterine growth restriction caused by underlying congenital cytomegalovirus infection. J Infect Dis 2014. [Epub ahead of print].

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The evaluation of inflammatory markers in umbilical cord blood.

We have read with great interest the article by Lausten-Thomsen et al. entitled "Inflammatory Markers in Umbilical Cord Blood from Small-For-Gestation...
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