Evaluation of Serum Interleukins-6, 8 and 10 Levels as Diagnostic Markers of Neonatal Infection and Possibility of Mortality

Document Type : Original Article


1 Department of Pediatrics, Ghaem Hospital, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Immunology Research Center, Avicenna Research Institute. Mashhad University of Medical Sciences, Mashhad, Iran

3 Biochemistry of Nutrition Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

4 Brighton & Sussex Medical School, Falmer, Brighton BN1 9PH, United Kingdom



Bacterial infection contributes substantially to neonatal morbidity and mortality. Early diagnosis of neonatal sepsis is difficult because clinical signs are non-specific. We have evaluated serum IL-6, 8 and 10 as potential early diagnostic markers of neonatal infection and their relationship to mortality rate and poor prognosis.
Materials and Methods
: A total of 84 infants, aged ≥ 72 hr were enrolled in this prospective case-control trial. The case group (n=41) included babies with clinical and laboratory findings compatible with sepsis and/or positive blood or cerebrospinal fluid cultures. The control group (n=43) included healthy infants. IL-6, 8 and 10 were measured for all infants. Receiver-operating characteristic (ROC) curves were used for the determination of thresholds.
: Statistically significant differences were observed between control and case groups for serum median level of IL-6, 8 and 10 (P<0.001). IL-6 cut-off values of 10.85 Pg/ml for discriminating between cases and controls and 78.2 Pg/ml for predicting mortality are suggested. IL-8 at a cut-off value of 60.05 Pg/ml was valuable for differentiation of definite versus indefinite infection.
: Evaluating the IL-6, 8 and 10 simultaneously, could improve the sensitivity and specificity of early diagnosis of the neonatal sepsis. Regarding our results, interleukin 6 had the greatest value for predicting infection and possible mortality, whereas IL-8 was valuable for diagnosing definitive infection.


1. Remington J, Klein J. Current concepts of infections of the fetus and newborn infant. In: JS R, JO K, editors. Infectious Diseases of the Fetus and Newborn Infants. Philadelphia: PA: WB Saunders; 1995. p. 1-19.
2. Stoll BJ, Gordon T, Korones SB, Shankaran S, Tyson JE, Bauer CR,
et al. Early-onset sepsis in very low birth weight neonates: a report from the National Institute of Child Health and Human Development Neonatal Research Network. J Pediatr 1996; 129:72-80.
3. Verboon-Maciolek MA, Thijsen SF, Hemels MA, Menses M, van Loon AM, Krediet TG,
et al. Inflammatory mediators for the diagnosis and treatment of sepsis in early infancy. Pediatr Res 2006; 59:457-461.
4. Adib M, Bakhshiani Z, Navaei F, Saheb Fosoul F, Fouladi S, Kazemzadeh H. Procalcitonin: a reliable marker for the diagnosis of neonatal sepsis. Iran J Basic Med Sci 2012; 15:777-782.
5. Fanaroff A, Martin R. Neonatal perinatal medicine. 8th ed. Mosby; 2006.p.791-799.
6. MacDonald M, Seshia M, Mullet M. Avery's Neonatology, Neonatal pathophysiology and management of the newborn. 6th ed. Philadelphia: LippincottWilliams&Wilkins; 2005.p.1236-1251.
7. Ng PC, Cheng SH, Chui KM, Fok TF, Wong MY, Wong W,
et al. Diagnosis of late onset neonatal sepsis with cytokines, adhesion molecule, and C-reactive protein in preterm very low birthweight infants. Arch Dis Child Fetal Neonatal Ed 1997; 77:F221-227.
8. Berger C, Uehlinger J, Ghelfi D, Blau N, Fanconi S. Comparison of C-reactive protein and white blood cell count with differential in neonates at risk for septicaemia. Eur J Pediatr 1995; 154:138-144.
9. Boskabadi H, Maamouri G, Sadeghian MH, Ghayour-Mobarhan M, Heidarzade M, Shakeri MT, Ferns G.Early diagnosis of perinatal asphyxia by nucleated red blood cell count: a case-control study. Arch Iran Med. 2010 Jul;13(4):275-81.
10. Gonzalez BE, Mercado CK, Johnson L, Brodsky NL, Bhandari V. Early markers of late-onset sepsis in premature neonates: clinical, hematological and cytokine profile. J Perinat Med 2003; 31:60-68.
11. Ng PC. Diagnostic markers of infection in neonates. Arch Dis Child Fetal Neonatal Ed 2004; 89:F229-235.
12. Murray BE. Can antibiotic resistance be controlled? N Engl J Med 1994; 330:1229-1230.
13. Ng PC, Cheng SH, Chui KM, Fok TF, Wong MY, Wong W,
et al. Diagnosis of late onset neonatal sepsis with cytokines, adhesion molecule, and C-reactive protein in preterm very low birthweight infants. Arch Dis Child Fetal Neonatal 1997; 77:221-227.
14. Bhartiya D, Kapadia C, Sanghvi K, Singh H, Kelkar R, Merchant R. Preliminary studies on IL-6 levels in healthy and septic Indian neonates. Indian Pediatr 2000; 37:1361-1367.
15. Schultz C, Rott C, Temming P, Schlenke P, Moller JC, Bucsky P. Enhanced interleukin-6 and interleukin-8 synthesis in term and preterm infants. Pediatr Res 2002; 51:317-322.
16. Mehr S, Doyle LW. Cytokines as markers of bacterial sepsis in newborn infants: a review. Pediatr Infect Dis J 2000; 19:879-887.
17. Buck C, Bundschu J, Gallati H, Bartmann P, Pohlandt F. Interleukin-6: a sensitive parameter for the early diagnosis of neonatal bacterial infection. Pediatrics 1994; 93:54-58.
18. Maamouri G, Boskabadi H, Tavakkolafshari J, Shakeri M. Evaluation Quantities Interleukin 6 in diagnosis of Neonatal sepsis. Med J Mashad Univ Med Sci 2006; 93:253-260.
19. Krueger M, Nauck MS, Sang S, Hentschel R, Wieland H, Berner R. Cord blood levels of interleukin-6 and interleukin-8 for the immediate diagnosis of early-onset infection in premature infants. Biol Neonate 2001; 80:118-123.
20. Romagnoli C, Frezza S, Cingolani A, De Luca A, Puopolo M, De Carolis MP,
et al. Plasma levels of interleukin-6 and interleukin-10 in preterm neonates evaluated for sepsis. Eur J Pediatr 2001; 160:345-350.
21. Edgar JD, Wilson DC, McMillan SA, Crockard AD, Halliday MI, Gardiner KR,
et al. Predictive value of soluble immunological mediators in neonatal infection. Clin Sci 1994; 87:165-171.
22. Kocabas E, Sarikcioglu A, Aksaray N, Seydaoglu G, Seyhun Y, Yaman A. Role of procalcitonin, C-reactive
Boskabadi et al Interleukins-6, 8 and 10 in Neonatal Infection
Iran J Basic Med Sci, Vol. 16, No. 12, Dec 2013
protein, interleukin-6, interleukin-8 and tumor necrosis factor-alpha in the diagnosis of neonatal sepsis. Turk J Pediatr 2007; 49:7-20.
23. Boskabadi H, Maamouri G, Afshari JT, Ghayour-Mobarhan M, Shakeri MT. Serum interleukin 8 level as a diagnostic marker in late neonatal sepsis. Iran J Pediatr 2010; 20:41-47.
24. Franz AR, Steinbach G, Kron M, Pohlandt F. Reduction of unnecessary antibiotic therapy in newborn infants using interleukin-8 and C-reactive protein as markers of bacterial infections. Pediatrics 1999; 104:447-453.
25. Schollin J. Interleukin-8 in neonatal sepsis. Acta Pediatr 2001; 90:961-962.
26. Boskabadi H, Maamouri GA, Ghayour-Mobarhan M, Tavakkol Afshari J, Shakeri MT, Ferns GAA. Early diagnosis of late neonatal sepsis by measuring interleukin 10: A case control study. J Neonatol 2011; 25:82-86.