A comparison of blood and cerebrospinal fluid cytokines (IL-1β, IL-6, IL-18, TNF-α) in neonates with perinatal hypoxia

  • Darinka Šumanović-Glamuzina Department of Neonatology and Intensive Care, Clinic for Child Diseases, University Hospital Mostar, Mostar, Bosnia and Herzegovina
  • Filip Čulo Physiology Department, School of Medicine, University of Zagreb, Zagreb, Croatia
  • Melanie Ivana Čulo Department of Clinical Immunology and Rheumathology, University Hospital Dubrava, Zagreb, Croatia
  • Paško Konjevoda NMR Department, Institute Ruđer Bošković, Zagreb, Croatia
  • Marjana Jerković-Raguž Department of Neonatology and Intensive Care, Clinic for Child Diseases, University Hospital Mostar, Mostar, Bosnia and Herzegovina
Keywords: Neonates, cytokines, perinatal hypoxia, hypoxic-ischemic encephalopathy, neurological outcome, IL-1β, IL-6, IL-18, TNF-α


Perinatal hypoxia-ischemia is a specific and important pathological event in neonatal care practice. The data on relationship between the concentrations of cytokines in blood and cerebrospinal fluid (CSF) and perinatal brain injury are scarce. The aim of this study is to evaluate changes in interleukin (IL-1β, IL-6, and IL-18) and tumor necrosis factor alpha (TNF-α) levels in newborns with perinatal hypoxia (PNH). CSF and serum samples of 35 term and near-term (35-40 weeks) newborns with PNH, at the age of 3-96 hours, were analyzed using enzyme-linked immunosorbent assay. Control group consisted of 25 non-asphyxic/non-hypoxic infants of the same age sampled for clinically suspected perinatal meningitis, but proven negative and healthy otherwise. The cytokine values in CSF and serum samples were determined in relation to initial hypoxic-ischemic encephalopathy (HIE) staged according the Sarnat/Sarnat method, and compared with neurological outcome at 12 months of age estimated using Amiel-Tison procedure. The concentrations of IL-6 and TNF-α in serum of PNH patients were significantly higher compared to control group (p = 0.0407 and p = 0.023, respectively). No significant difference between average values of cytokines in relation to the stage of HIE was observed. Significantly higher levels of IL-6 and IL-18 corresponded to a mildly abnormal neurological outcome, while higher levels of IL-6 and TNF-α corresponded to a severely abnormal neurological outcome, at 12 months of age. Elevated serum levels of IL-6 and TNF-α better corresponded with hypoxia/ischemia compared to CSF values, within 96 hours of birth. Also, higher serum levels of IL-6, TNF-α, and IL-18 corresponded better with abnormal neurological outcome at 12 months of age, compared to CSF values.


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Author Biographies

Darinka Šumanović-Glamuzina, Department of Neonatology and Intensive Care, Clinic for Child Diseases, University Hospital Mostar, Mostar, Bosnia and Herzegovina
Department of Neonatology and Intensive Care
Filip Čulo, Physiology Department, School of Medicine, University of Zagreb, Zagreb, Croatia
Physiology Department
Melanie Ivana Čulo, Department of Clinical Immunology and Rheumathology, University Hospital Dubrava, Zagreb, Croatia
Department of Clinical Immunology and Rheumathology
Paško Konjevoda, NMR Department, Institute Ruđer Bošković, Zagreb, Croatia
NMR Department
Marjana Jerković-Raguž, Department of Neonatology and Intensive Care, Clinic for Child Diseases, University Hospital Mostar, Mostar, Bosnia and Herzegovina
Department of Neonatology and Intensive Care


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A comparison of blood and cerebrospinal fluid cytokines (IL-1β, IL-6, IL-18, TNF-α) in neonates with perinatal hypoxia
How to Cite
Šumanović-Glamuzina D, Čulo F, Čulo MI, Konjevoda P, Jerković-Raguž M. A comparison of blood and cerebrospinal fluid cytokines (IL-1β, IL-6, IL-18, TNF-α) in neonates with perinatal hypoxia. Bosn J of Basic Med Sci [Internet]. 2017Aug.20 [cited 2020Mar.29];17(3):203-10. Available from: http://www.bjbms.org/ojs/index.php/bjbms/article/view/1381