American Journal of Clinical Medicine Research
ISSN (Print): 2328-4005 ISSN (Online): 2328-403X Website: Editor-in-chief: Dario Galante
Open Access
Journal Browser
American Journal of Clinical Medicine Research. 2019, 7(1), 26-30
DOI: 10.12691/ajcmr-7-1-5
Open AccessArticle

Relationship between Serum Interleukin-6 Levels and Bronchopulmonary Dysplasia in Preterm Infants at 28-34 Weeks’ Gestation with Respiratory Distress Syndrome

Ayu Alia1, , Fiva A Kadi1, Tetty Yuniati1, Aris Primadi1, Sjarief Hidajat1 and Abdurachman Sukadi1

1Department of Child Health, Universitas Padjadjaran, Bandung, Indonesia

Pub. Date: February 25, 2019

Cite this paper:
Ayu Alia, Fiva A Kadi, Tetty Yuniati, Aris Primadi, Sjarief Hidajat and Abdurachman Sukadi. Relationship between Serum Interleukin-6 Levels and Bronchopulmonary Dysplasia in Preterm Infants at 28-34 Weeks’ Gestation with Respiratory Distress Syndrome. American Journal of Clinical Medicine Research. 2019; 7(1):26-30. doi: 10.12691/ajcmr-7-1-5


Respiratory distress syndrome (RDS) remains a major cause of mortality and morbidity among preterm infants, especially in developing countries. Up to 40% of those infants who do survive RDS may develop bronchopulmonary dysplasia (BPD). The aim of this study is to find out the relationship between serum IL-6 levels and BPD in preterm infants at 28–34 weeks’ gestation with RDS. A cross sectional study was carried out in Department of Child Health Hasan Sadikin General Hospital Bandung in June–September 2018. Serum samples collected within 6–12 hours after birth. Respiratory distress syndrome was diagnosed on the basis of radiographic findings, respiratory distress, and an increasing oxygen requirement. Bronchopulmonary dysplasia was diagnosed based on the requirement of supplemented oxygen by at least 28 days at 36 weeks of post menstrual age (PMA). Serum IL-6 levels were measured using enzyme‑linked immunosorbent assay (ELISA). Data was analyzed using logistic regression. Sixty-eight neonates were studied. Ten developed BPD and 58 were not. Based on logistic regression showed that an increase of 1 pg/mL of serum IL-6 levels from the normal values examined at 6–12 hours after birth in preterm infants at 28–34 weeks’ gestation with RDS would increase log odds of BDP by 0.005 (p = 0.031) after adjustment for confounding factors of birth weight and gestational age. Increased in serum IL-6 levels within 6–12 hours after birth in preterm infants at 28–34 weeks’ gestation with RDS was associated with an increased risk of BPD.

respiratory distress syndrome preterm infants bronchopulmonary dysplasia cytokine interleukin-6

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit


[1]  Holme N, Chetcuti P. The pathophysiology of respiratory distress syndrome in neonates. Pediatric and child health. 2012; 22: 507-512.
[2]  Hermansen CL, Lorah KN. Respiratory distres in newborn. Am Fam Physician 2007; 76: 987-994.
[3]  Jackson JC. Respiratory distress in the preterm infant. In: Gleason CA, Devaskar SU, editor. Avery’s Disease of The Newborn. 9th Edition. Elsevier Saunders Inc. 2012. p. 644-657.
[4]  Guttentag S. Respiratory Distress Syndrome. In: Eichenwald E, Hansen A, Martin C, Stark A, editors. Manual of Neonatal care, 8th Edition. Wolters Kluwer. 2017. p. 437-445
[5]  Speer CP. Neonatal respiratory distress syndrome: an inflammatory disease? Neonatology. 2011;99:316-319.
[6]  Hammoud MS, Raghupathy R, Barakat N, Eltomi H, Elsori D. Cytokine profile at birth and the risk of developing severe respiratory distress and chronic lung disease. J Res Med Sci, 2017; 22: 62.
[7]  Varvarigou AA, Thomas I, Rodi M, Economou I, Mantagos S, Mouzaki A. Respiratory distress syndrome (RDS) in premature infants is underscored by the magnitude of Th1 cytokine polarization. Cytokine. 2012; 58: 355-360.
[8]  Rivera L, Siddaiah R, Oji-Mmuo C, Silveyra GR, Silveyra P. Biomarkers for bronchopulmonary dysplasia in the preterm infant. Front. Pediatr. 2016;4: 33.
[9]  Illiodromiti Z, Zygouris D, Sifakis S, Pappa KI, Tsikouras P, Salakos N, dkk. Acute lung injury inpreterm fetuses and neonates: mechanisms and molecular pathway. J Maternal Fetal Neonatal Med. 2013. [Online]. Available: [Accessed Oct. 25, 2017].
[10]  Balany J, Bhandari V. Understanding the impact of infection, inflammation, and their persistence in the pathogenesis of bronchopulmonary dysplasia. Front. Med. 2015; 2(90): 1-10.
[11]  Koksal N, Kayik B, Cetinkaya M, Ozkan H, Budak F, Kilic S, dkk. Value of serum and bronchoalveolar fluid lavage pro-and anti-inflammatory cytokine levels for predicting bronchopulmonary dysplasia in premature infants. Eur. Cytokine Netw. 2012; 23: 29-35.
[12]  Jobe, A.H. Mechanisms of lung injury and bronchopulmonary dysplasia. Am. J. Perinatol. 2016; 33: 1076-1078.
[13]  Niedermaier S, Hilgendorrf A. Bronchopulmonary dysplasia-an overview about pathophysiologic concepts. Molecular and Cellular Pediatrics. 2015; 2: 1-7.
[14]  Eric Z, Konjevic S. Proinflammatory cytokines in a newborn: a literature review. Signa Vitae. 2017; 13: 10-13.
[15]  Chiesa C, Pacifico L, Natale F, Hofer N, Osborn JF, Resch B. Fetal and early neonatal interleukin-6 response. Cytokine. 2015.
[16]  Tanaka T, Kishimoto T. Targeting interleukin-6: all the way to treat autoimmune and inflammatory diseases. Int. J. Biol. Sci. 2012; 8: 1227-36.
[17]  Lusyati S, Hulzebos CV, Zandvoort J, Sauer PJ. Levels of 25 cytokines in the first seven days of life in newborn infants. BMC Research Notes. 2013. 6:547.
[18]  Ambalavan N, Carlo WA, D’Angio CT, McDonald SA, Das A, Schendel D, dkk. Cytokines associated with bronchopulmonary dysplasia or death in extremely low birt weight infants. Pediatrics. 2009; 123: 1132-1141.
[19]  Sorokin Y, Romero R, Mele L, Iams JD, Peaceman AM, Leveno KJ, dkk. Umbilical cord serum interleukin-6, c-reactive protein, and myeloperoxidase concentrations at birth and association with neonatal morbidities and long term neurodevelopmental outcomes. Am J Perinatol. 2014; 31: 717-726.
[20]  Paananen R, Husa AK, Voulteennaho R. Blood cytokines during the perinatal period in very premature infants: relationship of inflammatory response and bronchopulmonary dysplasia. J Pediatr. 2009; 154: 39.
[21]  Tian XY, Zhang XD, Li QL, Shen Y, Zheng J. Biological markers in cord bloodfor prediction of bronchopulmonary dysplasia in premature infants. Clin Exp Obstet Gynecol. 2014; 41: 313-318.
[22]  Elabscience. Human interleukin 6 ELISA Kit. Catalog no: E-EL-H0102. 7th Edition. 2017.
[23]  Kair LR, Leonard DT, Anderson JM. Bronchopulmonary dysplasia. Pediatrics in Review. 2012; 33: 255-263.
[24]  Condo V, Cipriani S, Colnaghi M, Bellu R, Zanini R, Bulfoni C, dkk. Neonatal respiratory distress syndrome: are risk factors the same in preterm and term infants? J Matern Fetal Neonatal Med. 2017; 30(11): 1267-1272.
[25]  Liu J., Yang N, Liu Y. High-risk Factors of Respiratory Distress Syndrome in Term Neonates: A Retrospective Case-control Study. Balkan Med J 2014; 31: 64-68.
[26]  Zysman-Colman Z, Tremblay GM, Bandeali S, Landry JS. Bronchopulmonary dysplasia–trends over three decades. Pediatr. Child Health. 2013; 18: 86-90.
[27]  Torchin H, Ancel P, Goffinet F, Hascoet JM, Truffert P, Tran D, dkk. Plasental complication and bronchopulmonary dysplasia EPIPAGE-2 cohort study. Pediatrics. 2016; 1 37(3): e20152163.
[28]  Yüce O, Biçer OS, Kavuncuoğlu S, Ozelgün B, Ongüt C. Prematurity, infection, mortality, morbidity and interleukins: the reason or the result of preterm labor? Minerva Pediatr. 2014; 66: 563-70.
[29]  Bouch S, O,Reilly M, Harding R, Sozo F. Neonatal exposure to mild hyperoxia causes persistent increases in oxidative stress and immune cells in the lungs of mice without altering lung structure. Ajplung. 2015; 309: L488-96.
[30]  Wang H, Jafri A, Martin RJ, Nnanabu J, Farver C, Prakash S, dkk. Severity of neonatal hyperoxia determines structural and functional changes indeveloping mouse airway. Ajplung. 2014; 307: L295-301.
[31]  Hsiao C, Chang J, Tsao L, Yang R, Chen H, Lee C, dkk. Correlates of elevated interleukin-6 and 8-hydroxy-2’-deoxyguanosine levels in tracheal aspirates from very low birth weight infants who develop bronchopulmonary dysplasia. Pediatrics and Neonatology. 2017; 58: 63-69.
[32]  Davidson LM, Berkelhamer SK. Bronchopulmonary dysplasia: chronic lung disease of infancy and long-term pulmonary outcomes. J. Clin. Med. 2017; 6: 4.
[33]  Berkelhamer SK, Kim GA, Radder JE, Wedgwood S, Czech L, Steinhorn RH, dkk. Developmental differences in hyperoxia-induced oxidative stress and cellular responses in the murine lung. Free Radic. Biol. Med. 2013; 61: 51-60.
[34]  Yee M, White RJ, Awad HA, Bates WA, McGrath-Morrow SA, O’Reilly MA. Neonatal hyperoxia causes pulmonary vascular disease and shortens life span in aging mice. Am. J. Pathol. 2011; 178: 2601-2610.
[35]  Datta A, Kim GA, Taylor JM, Gugino SF, Farrow KN, Schumacker PT, dkk. Mouse lung development and nox1 induction during hyperoxia are developmentally regulated and mitochondrial ros dependent. Am. J. physiol. Lung Cell. Mol. Physiol. 2015; 309: L369-L377.