Cord Blood Levels of IL-8, MCP-1 and MIP-1α as Possible Predictors of Late Sepsis Development in Preterm Neonates

ORIGINAL ARTICLE
Jelena Vucic, Karin Vasic, Sandra Stankovic, Voja Pavlovic

 

For citation: Vucic J, Vasic K, Stankovic S, Pavlovic V. Cord Blood Levels of IL-8, MCP-1 and MIP-1α as Possible Predictors of Late Sepsis Development in Preterm Neonates. International Journal of Biomedicine. 2026;16(3):339-345. doi:10.21103/Article16(3)_OA2

Originally published September 5, 2026

Abstract: 

Background: The immature immune system of preterm neonates is a key factor in increased vulnerability to infections and sepsis. Although neonatal sepsis requires diagnostic tests, evaluating some chemokines may help predict sepsis and support early diagnosis, improving clinical outcomes.

Methods and Results: In the current study, which involved 80 participants, we analyzed the role of interleukin 8 (IL-8), monocyte chemotactic protein 1 (MCP-1), and macrophage inflammatory protein 1α (MIP-1α) in cord and venous blood plasma with C-reactive protein (CRP) and procalcitonin (PCT) for sepsis prediction and development in premature neonates. Levels of IL-8 (in cord and venous blood plasma), together with MCP-1 and MIP-1α levels in cord blood, were markedly elevated (P<0.001) in sepsis groups (early and late onset sepsis), together with venous blood PCT levels (P<0.001), compared to premature neonates without sepsis. On the other hand, CRP levels showed no significant change in the evaluated groups compared to the control group (without sepsis development).

Conclusion: These findings suggest that levels of IL-8, MCP-1, and MIP-1α in cord blood, rather than venous blood levels, together with venous blood PCT values, may have a predictive role for late sepsis development in premature neonates. Additional studies are required to evaluate the role of complex multiple mediators in predicting neonatal sepsis and to avoid unnecessary antibiotic treatment with improved clinical outcomes.

Keywords: 
premature neonates • late sepsis • IL-8 • MCP-1 • MIP-1α
References: 
  1. Kim F, Polin RA, Hooven TA. Neonatal sepsis. BMJ. 2020 Oct 1;371:m3672. doi: 10.1136/bmj.m3672. PMID: 33004379.
  2. Kuzniewicz MW, Mukhopadhyay S, Li S, Walsh EM, Puopolo KM. Time to Positivity of Neonatal Blood Cultures for Early-onset Sepsis. Pediatr Infect Dis J. 2020 Jul;39(7):634-640. doi: 10.1097/INF.0000000000002632. PMID: 32379197.
  3. Zasada M, Lenart M, Rutkowska-Zapała M, Stec M, Czyz O, Mól N, Siedlar M, Kwinta P. Inflammasome function in monocyte subsets and a risk of late-onset sepsis in preterm very low birth weight neonates. Minerva Pediatr (Torino). 2022 Apr;74(2):121-131. doi: 10.23736/S2724-5276.18.05034-X. Epub 2018 Jan 29. PMID: 29381011.
  4. Miller JE, Higgins LD, Dong Y, Collins JE, Bean JF, Seitz AL, Katz JN, Jain NB. Association of Strength Measurement with Rotator Cuff Tear in Patients with Shoulder Pain: The Rotator Cuff Outcomes Workgroup Study. Am J Phys Med Rehabil. 2016 Jan;95(1):47-56. doi: 10.1097/PHM.0000000000000329. PMID: 26098921; PMCID: PMC4713123.
  5. Hsu HE, Abanyie F, Agus MSD, Balamuth F, Brady PW, Brilli RJ, Carcillo JA, Dantes R, Epstein L, Fiore AE, Gerber JS, Gokhale RH, Joyner BL Jr, Kissoon N, Klompas M, Lee GM, Macias CG, Puopolo KM, Sulton CD, Weiss SL, Rhee C. A National Approach to Pediatric Sepsis Surveillance. Pediatrics. 2019 Dec;144(6):e20191790. doi: 10.1542/peds.2019-1790. PMID: 31776196; PMCID: PMC6889946.
  6. Wurzel D, Neeland MR, Anderson J, Abo YN, Do LAH, Donato CM, Bines JE, Toh ZQ, Higgins RA, Jalali S, Cole T, Subbarao K, McMinn A, Dohle K, Haeusler GM, McNab S, Alafaci A, Overmars I, Clifford V, Lee LY, Daley AJ, Buttery J, Bryant PA, Burgner D, Steer A, Tosif S, Konstantinov IE, Duke T, Licciardi PV, Pellicci DG, Crawford NW. A case report describing the immune response of an infant with congenital heart disease and severe COVID-19. Commun Med (Lond). 2021 Nov 15;1:47. doi: 10.1038/s43856-021-00047-7. PMID: 35602234; PMCID: PMC9053208.
  7. Marchant EA, Kan B, Sharma AA, van Zanten A, Kollmann TR, Brant R, Lavoie PM. Attenuated innate immune defenses in very premature neonates during the neonatal period. Pediatr Res. 2015 Nov;78(5):492-7. doi: 10.1038/pr.2015.132. Epub 2015 Jul 17. PMID: 26186294; PMCID: PMC5059157.
  8. Goswami S, Gupta R, Ramji S. Flow Cytometry: An Important Diagnostic Tool in Critically Ill Preterm Neonates with Suspected Sepsis. Am J Perinatol. 2022 Apr;39(6):616-622. doi: 10.1055/s-0040-1718370. Epub 2020 Sep 29. PMID: 32992350.
  9. Segura-Cervantes E, Mancilla-Ramírez J, González-Canudas J, Alba E, Santillán-Ballesteros R, Morales-Barquet D, Sandoval-Plata G, Galindo-Sevilla N. Inflammatory Response in Preterm and Very Preterm Newborns with Sepsis. Mediators Inflamm. 2016;2016:6740827. doi: 10.1155/2016/6740827. Epub 2016 May 16. PMID: 27293317; PMCID: PMC4884838.
  10. Collins A, Weitkamp JH, Wynn JL. Why are preterm newborns at increased risk of infection? Arch Dis Child Fetal Neonatal Ed. 2018 Jul;103(4):F391-F394. doi: 10.1136/archdischild-2017-313595. Epub 2018 Jan 30. PMID: 29382648; PMCID: PMC6013388.
  11. Celik IH, Hanna M, Canpolat FE, Mohan Pammi. Diagnosis of neonatal sepsis: the past, present and future. Pediatr Res. 2022 Jan;91(2):337-350. doi: 10.1038/s41390-021-01696-z. Epub 2021 Nov 2. PMID: 34728808; PMCID: PMC8818018.
  12. Goldstein B, Giroir B, Randolph A; International Consensus Conference on Pediatric Sepsis. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med. 2005 Jan;6(1):2-8. doi: 10.1097/01.PCC.0000149131.72248.E6. PMID: 15636651.
  13. Bogale A, Borko UD, Abreha S, Balta B. Determinants of mortality among preterm neonates admitted at Wolaita Sodo University Comprehensive Specialized Hospital, southern Ethiopia: An unmatched case-control study. PLoS One. 2024 Dec 2;19(12):e0314632. doi: 10.1371/journal.pone.0314632. PMID: 39621711; PMCID: PMC11611175.
  14. Kucova P, Kantor L, Fiserova K, Lasak J, Röderova M, Kolar M. Bacterial Pathogens and Evaluation of a Cut-Off for Defining Early and Late Neonatal Infection. Antibiotics (Basel). 2021 Mar 9;10(3):278. doi: 10.3390/antibiotics10030278. PMID: 33803288; PMCID: PMC7998728.
  15. Fenton TR, Merlino Barr S, Elmrayed S, Alshaikh B. Expected and Desirable Preterm and Small Infant Growth Patterns. Adv Nutr. 2024 Jun;15(6):100220. doi: 10.1016/j.advnut.2024.100220. Epub 2024 Apr 24. PMID: 38670164; PMCID: PMC11251411.
  16. Yadav P, Yadav SK. Progress in Diagnosis and Treatment of Neonatal Sepsis: A Review Article. JNMA J Nepal Med Assoc. 2022 Mar 11;60(247):318-324. doi: 10.31729/jnma.7324. PMID: 35633256; PMCID: PMC9226748.
  17. Kurul Ş, Beckers FLM, Vermeulen MJ, Suurland J, Hasbek JE, Ramakers CRB, Simons SHP, Reiss IKM, Taal HR. Inflammation, sepsis severity and neurodevelopmental outcomes of late-onset sepsis in preterm neonates. Pediatr Res. 2023 Dec;94(6):2026-2032. doi: 10.1038/s41390-023-02742-8. Epub 2023 Jul 19. PMID: 37468719.
  18. Shah J, Balasubramaniam T, Yang J, Shah PS. Leukopenia and Neutropenia at Birth and Sepsis in Preterm Neonates of <32 Weeks’ Gestation. Am J Perinatol. 2022 Jul;39(9):965-972. doi: 10.1055/s-0040-1721133. Epub 2020 Nov 23. PMID: 33231269.
  19. Ebenebe CU, Hesse F, Blohm ME, Jung R, Kunzmann S, Singer D. Diagnostic accuracy of interleukin-6 for early-onset sepsis in preterm neonates. J Matern Fetal Neonatal Med. 2021 Jan;34(2):253-258. doi: 10.1080/14767058.2019.1606194. Epub 2019 Apr 29. PMID: 30966828.
  20. Bethou A, Bhat BV. Neonatal Sepsis-Newer Insights. Indian J Pediatr. 2022 Mar;89(3):267-273. doi: 10.1007/s12098-021-03852-z. Epub 2021 Jun 25. PMID: 34170492.
  21. Cantey JB, Lee JH. Biomarkers for the Diagnosis of Neonatal Sepsis. Clin Perinatol. 2021 Jun;48(2):215-227. doi: 10.1016/j.clp.2021.03.012. PMID: 34030810.
  22. Mota RB, Soares P, Guimarães H. Assessment of a score’s performance in predicting positive culture studies in preterm neonates with clinical suspicion of sepsis. J Mother Child. 2022 Apr 1;25(2):119-122. doi: 10.34763/jmotherandchild.20212502.d-21-00019. PMID: 34786899; PMCID: PMC8976589.
  23. Rao JG, Sarangi R, Das R, Nanda D, Jena PP, Krishnegowda VK. Outcomes and antimicrobial usage in preterm neonates < 34 weeks gestation with culture-negative neonatal sepsis: a prospective observational study. BMC Infect Dis. 2025 Dec 6;26(1):44. doi: 10.1186/s12879-025-12288-1. PMID: 41353525; PMCID: PMC12797939.
  24. Hibbert J, Strunk T, Simmer K, Richmond P, Burgner D, Currie A. Plasma cytokine profiles in very preterm infants with late-onset sepsis. PLoS One. 2020 May 14;15(5):e0232933. doi: 10.1371/journal.pone.0232933. PMID: 32407417; PMCID: PMC7224469.
  25. Glaser MA, Hughes LM, Jnah A, Newberry D. Neonatal Sepsis: A Review of Pathophysiology and Current Management Strategies. Adv Neonatal Care. 2021 Feb 1;21(1):49-60. doi: 10.1097/ANC.0000000000000769. PMID: 32956076.
  26. Yochpaz S, Friedman N, Zirkin S, Blumovich A, Mandel D, Marom R. C-reactive protein in early-onset neonatal sepsis - a cutoff point for CRP value as a predictor of early-onset neonatal sepsis in term and late preterm infants early after birth? J Matern Fetal Neonatal Med. 2022 Dec;35(23):4552-4557. doi: 10.1080/14767058.2020.1856068. Epub 2020 Dec 6. PMID: 33280469.
  27. Macallister K, Smith-Collins A, Gillet H, Hamilton L, Davis J. Serial C-Reactive Protein Measurements in Newborn Infants without Evidence of Early-Onset Infection. Neonatology. 2019;116(1):85-91. doi: 10.1159/000497237. Epub 2019 May 21. PMID: 31112949.
  28. Balayan S, Chauhan N, Chandra R, Kuchhal NK, Jain U. Recent advances in developing biosensing based platforms for neonatal sepsis. Biosens Bioelectron. 2020 Dec 1;169:112552. doi: 10.1016/j.bios.2020.112552. Epub 2020 Aug 25. PMID: 32931992.
  29. Brown JVE, Meader N, Wright K, Cleminson J, McGuire W. Assessment of C-Reactive Protein Diagnostic Test Accuracy for Late-Onset Infection in Newborn Infants: A Systematic Review and Meta-analysis. JAMA Pediatr. 2020 Mar 1;174(3):260-268. doi: 10.1001/jamapediatrics.2019.5669. Erratum in: JAMA Pediatr. 2020 Jun 1;174(6):625. doi: 10.1001/jamapediatrics.2020.0950. PMID: 32011640; PMCID: PMC7042944.
  30. Kordek A, Łoniewska B, Podraza W, Nikodemski T, Rudnicki J. Usefulness of estimation of blood procalcitonin concentration versus C-reactive protein concentration and white blood cell count for therapeutic monitoring of sepsis in neonates. Postepy Hig Med Dosw (Online). 2014 Dec 21;68:1516-23. doi: 10.5604/17322693.1133101. PMID: 25531715.
  31. Sharma D, Farahbakhsh N, Shastri S, Sharma P. Biomarkers for diagnosis of neonatal sepsis: a literature review. J Matern Fetal Neonatal Med. 2018 Jun;31(12):1646-1659. doi: 10.1080/14767058.2017.1322060. Epub 2017 May 7. PMID: 28427289.
  32. Wacker C, Prkno A, Brunkhorst FM, Schlattmann P. Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis. Lancet Infect Dis. 2013 May;13(5):426-35. doi: 10.1016/S1473-3099(12)70323-7. Epub 2013 Feb 1. PMID: 23375419.
  33. Eichberger J, Resch E, Resch B. Diagnosis of Neonatal Sepsis: The Role of Inflammatory Markers. Front Pediatr. 2022 Mar 8;10:840288. doi: 10.3389/fped.2022.840288. PMID: 35345614; PMCID: PMC8957220.
  34. Lisowska KA. The Role of Interleukin-8 (IL-8) in Treatment-Resistant Depression: A Review of Mechanisms, Biomarker Potential, and Therapeutic Implications. Int J Mol Sci. 2025 Oct 16;26(20):10092. doi: 10.3390/ijms262010092. PMID: 41155383; PMCID: PMC12562488.
  35. Gibbons D, Fleming P, Virasami A, Michel ML, Sebire NJ, Costeloe K, Carr R, Klein N, Hayday A. Interleukin-8 (CXCL8) production is a signatory T cell effector function of human newborn infants. Nat Med. 2014 Oct;20(10):1206-10. doi: 10.1038/nm.3670. Epub 2014 Sep 21. PMID: 25242415.
  36. Lusyati S, Hulzebos CV, Zandvoort J, Sukandar H, Sauer PJ. Cytokines patterns in newborn infants with late onset sepsis. J Neonatal Perinatal Med. 2013;6(2):153-63. doi: 10.3233/NPM-1364112. PMID: 24246518.
  37. Chen X, Zhang X, Xue R, Mi L, Liu Y, Zhang G, Bu J, Bei F. Intrauterine inflammation exposure may increase the risk of late-onset sepsis in premature infants: a retrospective cohort study. Ital J Pediatr. 2025 Jul 10;51(1):218. doi: 10.1186/s13052-025-02040-5. PMID: 40640885; PMCID: PMC12247326.
  38. Gustafsson A, Johansson E, Henckel E, Olin A, Rodriguez L, Brodin P, Lange S, Bohlin K. Antisecretory factor in breastmilk is associated with reduced incidence of sepsis in preterm infants. Pediatr Res. 2024 Feb;95(3):762-769. doi: 10.1038/s41390-023-02909-3. Epub 2023 Nov 24. PMID: 38001236; PMCID: PMC10899102.
  39. Strunk T, Hibbert J, Doherty D, Nathan E, Simmer K, Richmond P, Currie A, Burgner D. Impaired Cytokine Responses to Live Staphylococcus epidermidis in Preterm Infants Precede Gram-positive, Late-onset Sepsis. Clin Infect Dis. 2021 Jan 27;72(2):271-278. doi: 10.1093/cid/ciaa063. PMID: 31960030.
  40. Lindner U, Tutdibi E, Binot S, Monz D, Hilgendorff A, Gortner L. Levels of cytokines in umbilical cord blood in small for gestational age preterm infants. Klin Padiatr. 2013 Mar;225(2):70-74. doi: 10.1055/s-0033-1334879. Epub 2013 Mar 22. PMID: 23526611.
  41. Sugitharini V, Prema A, Berla Thangam E. Inflammatory mediators of systemic inflammation in neonatal sepsis. Inflamm Res. 2013 Dec;62(12):1025-34. doi: 10.1007/s00011-013-0661-9. Epub 2013 Sep 8. PMID: 24013483.
  42. Otsubo Y, Hashimoto K, Kanbe T, Sumi M, Moriuchi H. Association of cord blood chemokines and other biomarkers with neonatal complications following intrauterine inflammation. PLoS One. 2017 May 22;12(5):e0175082. doi: 10.1371/journal.pone.0175082. PMID: 28531215; PMCID: PMC5439663.
  43. Anderson J, Thang CM, Thanh LQ, Dai VTT, Phan VT, Nhu BTH, Trang DNX, Trinh PTP, Nguyen TV, Toan NT, Harpur CM, Mulholland K, Pellicci DG, Do LAH, Licciardi PV. Immune Profiling of Cord Blood From Preterm and Term Infants Reveals Distinct Differences in Pro-Inflammatory Responses. Front Immunol. 2021 Nov 1;12:777927. doi: 10.3389/fimmu.2021.777927. PMID: 34790206; PMCID: PMC8591285.
  44. Morajker G, Patil AA, Ranya Raghavendra P, Datar A, Nair S, Dandekar Jain P, Balasubramanian H, Haribalakrishna A, Goyal M, Kabra NS. Urinary immune biomarkers for late-onset sepsis in preterm very low birth weight neonates - a diagnostic accuracy study. J Perinat Med. 2025 Oct 7;54(3):630-636. doi: 10.1515/jpm-2025-0342. PMID: 41052967.
  45. de Jong E, Strunk T, Burgner D, Lavoie PM, Currie A. The phenotype and function of preterm infant monocytes: implications for susceptibility to infection. J Leukoc Biol. 2017 Sep;102(3):645-656. doi: 10.1189/jlb.4RU0317-111R. Epub 2017 Jun 19. PMID: 28630102.

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Received June 12, 2026.
Accepted August 4, 2026.
© 2026 The Author(s). International Journal of Biomedicine is published by IMRDC. This is an open access article under the CC BY-NC-ND 4.0 license.