Am J Perinatol 2008; 25(10): 629-636
DOI: 10.1055/s-0028-1090585
© Thieme Medical Publishers

Utility of Interleukin-12 and Interleukin-10 in Comparison with Other Cytokines and Acute-Phase Reactants in the Diagnosis of Neonatal Sepsis

Catherine Sherwin1 , Roland Broadbent1 , Sarah Young2 , Janie Worth3 , Frances McCaffrey4 , Natalie J. Medlicott5 , David Reith1
  • 1Department of Women's and Children's Health, Dunedin School of Medicine, Dunedin, New Zealand
  • 2Department of Microbiology and Immunology, Dunedin, New Zealand
  • 3Otago District Health Board, Dunedin, New Zealand
  • 4NICU, University of Otago, Dunedin, New Zealand
  • 5School of Pharmacy, University of Otago, Dunedin, New Zealand
Further Information

Publication History

Publication Date:
10 October 2008 (online)

ABSTRACT

We compared the test characteristics of interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12(p-70), tumor necrosis factor-α (TNF-α), procalcitonin (PCT), C-reactive protein (CRP), and full blood count (FBC) in the diagnosis of neonatal sepsis. This prospective cohort study in the Neonatal Intensive Care Unit of Dunedin hospital of patients between July 1, 2002 and February 28, 2007 included 117 neonates commenced on antibiotics for 164 episodes of suspected sepsis. Blood cultures, FBC, CRP, IL-1β, IL-6, IL-8, IL-10, IL-12(p-70), TNF-α, and PCT were obtained at the time sepsis was first suspected and for the following 3 days. Receiver operator characteristics (ROC) plots and test characteristics were determined using culture-positive sepsis as the gold standard. At the time sepsis was first suspected, the most promising individual test was IL-12(p70) with an area under the curve (95% confidence interval [CI]) for the ROC of 0.74 (0.63 to 0.86), which (with a cutoff at 75 pg/mL) had a sensitivity (95% CI) of 28% (20 to 36%) and a specificity of 98% (96 to 100%). IL-10 had a sensitivity of 17% (10 to 23%) and a specificity of 99% (97 to 100%). IL-10 and IL-12(p70) are promising diagnostic tests that can be used to confirm sepsis in neonates.

REFERENCES

  • 1 Toltzis P, Dul M J, Hoyen C et al.. Molecular epidemiology of antibiotic-resistant gram-negative bacilli in a neonatal intensive care unit during a nonoutbreak period.  Pediatrics. 2001;  108 1143-1148
  • 2 Parry G J, Tucker J S, Tarnow-Mordi W O. Relationship between probable nosocomial bacteraemia and organisational and structural factors in UK neonatal intensive care units.  Qual Saf Health Care. 2005;  14 264-269
  • 3 Mehr S S, Sadowsky J L, Doyle L W, Carr J. Sepsis in neonatal intensive care in the late 1990s.  J Paediatr Child Health. 2002;  38 246-251
  • 4 Stoll B J, Hansen N I, Adams-Chapman I et al.. Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection.  JAMA. 2004;  292 2357-2365
  • 5 Fowlie P W, Schmidt B. Diagnostic tests for bacterial infection from birth to 90 days: a systematic review.  Arch Dis Child Fetal Neonatal Ed. 1998;  78 F92-F98
  • 6 Malik A, Hui C P, Pennie R A, Kirpalani H. Beyond the complete blood cell count and C-reactive protein: a systematic review of modern diagnostic tests for neonatal sepsis.  Arch Pediatr Adolesc Med. 2003;  157 511-516
  • 7 Ng P C, Lam H S. Diagnostic markers for neonatal sepsis.  Curr Opin Pediatr. 2006;  18 125-131
  • 8 Hodge G, Hodge S, Haslam R et al.. Rapid simultaneous measurement of multiple cytokines using 100 microl sample volumes: association with neonatal sepsis.  Clin Exp Immunol. 2004;  137 402-407
  • 9 Martin H, Olander B, Norman M. Reactive hyperemia and interleukin 6, interleukin 8, and tumor necrosis factor-a in the diagnosis of early-onset neonatal sepsis.  Pediatrics. 2001;  108(4) E61
  • 10 Pourcyrous M, Korones S B, Crouse D, Bada H S. Interleukin-6, C-reactive protein, and abnormal cardiorespiratory responses to immunization in premature infants.  Pediatrics. 1998;  101(3) E3
  • 11 Romagnoli C, Frezza S, Cingolani A et al.. Plasma levels of interleukin-6 and interleukin-10 in preterm neonates evaluated for sepsis.  Eur J Pediatr. 2001;  160 345-350
  • 12 Ng P C, Li K, Chui K M et al.. IP-10 is an early diagnostic marker for identification of late-onset bacterial infection in preterm infants.  Pediatr Res. 2007;  61 93-98
  • 13 Ng P C, Cheng S H, Chui K M 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-F227
  • 14 Dollner H, Vatten L, Austgulen R. Early diagnostic markers for neonatal sepsis: comparing C-reactive protein, interleukin-6, soluble tumour necrosis factor receptors and soluble adhesion molecules.  J Clin Epidemiol. 2001;  54 1251-1257
  • 15 Santana Reyes C, Garcia-Munoz F, Reyes D, Gonzalez G, Dominguez C, Domenech E. Role of cytokines (interleukin-1beta, 6, 8, tumour necrosis factor-alpha, and soluble receptor of interleukin-2) and C-reactive protein in the diagnosis of neonatal sepsis.  Acta Paediatr. 2003;  92 221-227
  • 16 Laborada G, Rego M, Jain A et al.. Diagnostic value of cytokines and C-reactive protein in the first 24 hours of neonatal sepsis.  Am J Perinatol. 2003;  20 491-501
  • 17 Messer J, Eyer D, Donato L, Gallati H, Matis J, Simeoni U. Evaluation of interleukin-6 and soluble receptors of tumor necrosis factor for early diagnosis of neonatal infection.  J Pediatr. 1996;  129 574-580
  • 18 Kuster H, Weiss M, Willeitner A E et al.. Interleukin-1 receptor antagonist and interleukin-6 for early diagnosis of neonatal sepsis 2 days before clinical manifestation.  Lancet. 1998;  352 1271-1277
  • 19 Franz A R, 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
  • 20 Silveira R C, Procianoy R S. Evaluation of interleukin-6, tumour necrosis factor-alpha and interleukin-1 beta for early diagnosis of neonatal sepsis.  Acta Paediatr. 1999;  88 647-650
  • 21 Mehr S S, Doyle L W, Rice G E, Vervaart P, Henschke P. Interleukin-6 and interleukin-8 in newborn bacterial infection.  Am J Perinatol. 2001;  18 313-323
  • 22 Enguix A, Rey C, Concha A, Medina A, Coto D, Dieguez M A. Comparison of procalcitonin with C-reactive protein and serum amyloid for the early diagnosis of bacterial sepsis in critically ill neonates and children.  Intensive Care Med. 2001;  27 211-215
  • 23 Resch B, Gusenleitner W, Muller W D. Procalcitonin and interleukin-6 in the diagnosis of early-onset sepsis of the neonate.  Acta Paediatr. 2003;  92 243-245
  • 24 Turner D, Hammerman C, Rudensky B, Schlesinger Y, Schimmel M S. The role of procalcitonin as a predictor of nosocomial sepsis in preterm infants.  Acta Paediatr. 2006;  95 1571-1576
  • 25 Franz A R, Kron M, Pohlandt F, Steinbach G. Comparison of procalcitonin with interleukin 8, C-reactive protein and differential white blood cell count for the early diagnosis of bacterial infections in newborn infants.  Pediatr Infect Dis J. 1999;  18 666-671
  • 26 Pavcnik-Arnol M, Hojker S, Derganc M. Lipopolysaccharide-binding protein in critically ill neonates and children with suspected infection: comparison with procalcitonin, interleukin-6, and C-reactive protein.  Intensive Care Med. 2004;  30 1454-1460
  • 27 Silveira R C, Procianoy R S. Interleukin-6 and tumor necrosis factor-alpha levels in plasma and cerebrospinal fluid of term newborn infants with hypoxic-ischemic encephalopathy.  J Pediatr. 2003;  143 625-629
  • 28 Chiesa C, Signore F, Assumma M et al.. Serial measurements of C-reactive protein and interleukin-6 in the immediate postnatal period: reference intervals and analysis of maternal and perinatal confounders.  Clin Chem. 2001;  47 1016-1022
  • 29 Jokic M, Guillois B, Cauquelin B et al.. Fetal distress increases interleukin-6 and interleukin-8 and decreases tumour necrosis factor-alpha cord blood levels in noninfected full-term neonates.  BJOG. 2000;  107 420-425
  • 30 Dembinski J, Behrendt D, Martini R, Heep A, Bartmann P. Modulation of pro- and anti-inflammatory cytokine production in very preterm infants.  Cytokine. 2003;  21 200-206
  • 31 Dammann O, Phillips T M, Allred E N et al.. Mediators of fetal inflammation in extremely low gestational age infants.  Cytokine. 2001;  13 234-239
  • 32 Schultz C, Rott C, Temming P, Schlenke P, Moller A JC, Bucsky P. Enhanced interleukin-6 and interleukin-8 synthesis in term and preterm infants.  Pediatr Res. 2002;  51 317-322
  • 33 Turner D, Hammerman C, Rudensky B, Schlesinger Y, Goia C, Schimmel M S. Procalcitonin in preterm infants during the first few days of life: introducing an age related nomogram.  Arch Dis Child Fetal Neonatal Ed. 2006;  91 F283-F286
  • 34 Ehl S, Gering B, Bartmann P, Hogel J, Pohlandt F. C-reactive protein is a useful marker for guiding duration of antibiotic therapy in suspected neonatal bacterial infection.  Pediatrics. 1997;  99 216-221
  • 35 Arnon S, Litmanovitz I, Regev R, Lis M, Shainkin-Kestenbaum R, Dolfin T. The prognostic virtue of inflammatory markers during late-onset sepsis in preterm infants.  J Perinat Med. 2004;  32 176-180
  • 36 Icagasioglu D. Serum C-reactive protein and interleukin-6 levels in neonatal sepsis.  Acta Medica (Hradec Kralove). 2002;  45 111-113
  • 37 Schultz C, Temming P, Bucsky P, Gopel W, Strunk T, Hartel C. Immature anti-inflammatory response in neonates.  Clin Exp Immunol. 2004;  135 130-136

David ReithM.B.B.S. F.R.A.C.P. Ph.D. 

Associate Professor, Dunedin School of Medicine, University of Otago

P.O. Box 913, Dunedin, New Zealand

Email: david.reith@stonebow.otago.ac.nz

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