Child's Nervous System

, Volume 35, Issue 4, pp 629–636 | Cite as

Tumor necrosis factor alpha and interleukin-1 beta levels in cerebrospinal fluid examination for the diagnosis of ventriculoperitoneal shunt-related ventriculitis

  • Semih K. OlgunerEmail author
  • Bulent Boyar
  • Derya Alabaz
  • Tahsin Erman
  • Kadir Oktay
  • Ali Arslan
  • Emre Bilgin
  • Ali Ihsan Okten
Original Article



Ventriculitis is known to develop after chronic inflammation and bacterial invasion of the ventricular surface with a recurrence of shunt infections. The aim of this study is to evaluate the diagnostic value of elevation in cerebrospinal fluid (CSF) interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) together with CSF culture and laboratory test results in the diagnosis of ventriculoperitoneal (VP) shunt-related ventriculitis, which is known to be more problematic than conventional shunt infection.


The study included a total of 34 patients with a VP shunt due to hydrocephalus, who presented with a headache, fever, and shunt infection at the Emergency Department and had a pre-diagnosis of ventriculitis. Nineteen patients were diagnosed with shunt-related infection or ventriculitis using the CSF obtained from the shunt pump. The IL-1β and TNF-α levels from the CSF samples of all patients were measured using the Micro ELISA immunoassay method.


CSF direct microscopic observation revealed that the mean cell count, IL-1β level, CRP level, and blood leukocyte level were higher in patients with ventriculitis compared to those diagnosed with shunt infection (p = 0.02, p = 0.009, p = 0.004, and p = 0.009, respectively). The probability of predicting positive culture outcome was 92.7% with 90.9% sensitivity and 82.6% specificity when IL-1β values exceeded 4.0 pg/ml. TNF-α values did not show a significant, reliable pattern compared to IL-1β.


IL-1β is a reliable parameter which shall be used in the diagnosis of ventriculitis by predicting positive culture outcome with high sensitivity and specificity.


Shunt infections Ventriculitis TNF-α IL-1β 


Authors’ contributions

Semih K. Olguner, Bulent Boyar, Derya Alabaz, and Tahsin Erman were involved in the study conception and design. Ali İhsan Okten, Ali Arslan, Emre Bilgin, and Kadir Oktay were responsible for the data analysis. All authors contributed to the discussion, interpreted the findings, helped write, reviewed/edited the manuscript for intellectual content, and read and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval and consent to participate

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics Committee of Çukurova Medical Faculty. All participants provided informed consent.


  1. 1.
    Asi-Bautista MC, Heidemann SM, Meert KL, Canady AI, Sarnaik AP (1997) Tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 concentrations in cerebrospinal fluid predict ventriculoperitoneal shunt infection. Crit Care Med 25:1713–1716CrossRefPubMedGoogle Scholar
  2. 2.
    Barichello T, dos Santos I, Savi GD, Simões LR, Silvestre T, Comim CM, Sachs D, Teixeira MM, Teixeira AL, Quevedo J (2010) TNF-α, IL-1β, IL-6, and cinc-1 levels in rat brain after meningitis induced by Streptococcus pneumoniae. J Neuroimmunol 221:42–45. CrossRefPubMedGoogle Scholar
  3. 3.
    Beer R, Lackner P, Pfausler B, Schmutzhard E (2008) Nosocomial ventriculitis and meningitis in neurocritical care patients. J Neurol 255:1617–1624. CrossRefPubMedGoogle Scholar
  4. 4.
    Belogurov AA, Ivanova OM, Lomakin YA, Ziganshin RH, Vaskina MI, Knorre VD, Klimova EA, Gabibov AG, Ivanov VT, Govorun VM (2016) Mediators and biomarkers of inflammation in meningitis: cytokine and peptidome profiling of cerebrospinal fluid. Biochemistry (Mosc) 81:1293–1302. CrossRefGoogle Scholar
  5. 5.
    Boeer K, Vogelsang H, Deufel T, Pfister W, Kiehntopf M (2011) Immediate diagnosis of ventriculits: evaluation of parameters independent of microbiological culture. Acta Neurochir 153:1797–1805. CrossRefPubMedGoogle Scholar
  6. 6.
    Chen K, Wu Y, Wang Q, Wang J, Li X, Zhao Z, Zhou J (2015) The methodology and pharmacokinetics study of intraventricular administration of vancomycin in patients with intracranial infections after craniotomy. J Crit Care 30:218.e1–218.e5. CrossRefGoogle Scholar
  7. 7.
    Cuchacovich M, Bueno D, Carvajal R, Bravo N, Aguillón JC, Catalán D, Soto L (2014) Clinical parameters and biomarkers for anti-TNF treatment prognosis in rheumatoid arthritis patients. Clin Rheumatol 33:1707–1714. CrossRefPubMedGoogle Scholar
  8. 8.
    Fida NM, Al-Mughales J, Farouq M (2006) Interleukin-1alpha, interleukin-6 and tumor necrosis factor-alpha levels in children with sepsis and meningitis. Pediatr Int 48:118–124. CrossRefPubMedGoogle Scholar
  9. 9.
    Friedrich EE, Sun LT, Natesan S, Zamora DO, Christy RJ, Washburn NR (2014) Effects of hyaluronic acid conjugation on anti-TNF-α inhibition of inflammation in burns. J Biomed Mater Res Part A 102:1527–1536. CrossRefGoogle Scholar
  10. 10.
    Gordon M, Ramirez P, Soriano A, Palomo M, Lopez-Ferraz C, Villarreal E, Meseguer S, Gomez MD, Folgado C, Bonastre J (2014) Diagnosing external ventricular drain-related ventriculitis by means of local inflammatory response: soluble triggering receptor expressed on myeloid cells-1. Crit Care 18:567. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Grandgirard D, Gäumann R, Coulibaly B, Dangy J-P, Sie A, Junghanss T, Schudel H, Pluschke G, Leib SL (2013) The causative pathogen determines the inflammatory profile in cerebrospinal fluid and outcome in patients with bacterial meningitis. Mediat Inflamm 2013:312476. doi:, 1, 12
  12. 12.
    Handa S (1992) Concentrations of interleukin-1 beta, interleukin-6, interleukin-8 and TNF-alpha in cerebrospinal fluid from children with septic or aseptic meningitis. Kurume Med J 39:257–265CrossRefPubMedGoogle Scholar
  13. 13.
    Krebs VLJ, Okay TS, Okay Y, Vaz FAC (2005) Tumor necrosis factor-alpha, interleukin-1beta and interleukin-6 in the cerebrospinal fluid of newborn with meningitis. Arq Neuropsiquiatr 63:7–13CrossRefPubMedGoogle Scholar
  14. 14.
    Laborada G, Cruz F, Nesin M (2005) Serial cytokine profiles in shunt-related ventriculitis treated with intraventricular vancomycin. Chemotherapy 51:363–365. CrossRefPubMedGoogle Scholar
  15. 15.
    Lifshutz JI, Johnson WD (2001) History of hydrocephalus and its treatments. Neurosurg Focus:11:1–11:5.
  16. 16.
    López-Cortés LF, Marquez-Arbizu R, Jimenez-Jimenez LM, Jimenez-Mejías E, Caballero-Granado FJ, Rey-Romero C, Polaina M, Pachón J (2000) Cerebrospinal fluid tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, and interleukin-8 as diagnostic markers of cerebrospinal fluid infection in neurosurgical patients. Crit Care Med 28:215–219CrossRefPubMedGoogle Scholar
  17. 17.
    Morris A, Low DE (1999) Nosocomial bacterial meningitis, including central nervous system shunt infections. Infect Dis Clin N Am 13:735–750CrossRefGoogle Scholar
  18. 18.
    Mukai AO, Krebs VLJ, Bertoli CJ, Okay TS (2006) TNF-alpha and IL-6 in the diagnosis of bacterial and aseptic meningitis in children. Pediatr Neurol 34:25–29. CrossRefPubMedGoogle Scholar
  19. 19.
    Mustafa MM, Mertsola J, Ramilo O, Sáez-Llorens X, Risser RC, McCracken GH (1989) Increased endotoxin and interleukin-1 beta concentrations in cerebrospinal fluid of infants with coliform meningitis and ventriculitis associated with intraventricular gentamicin therapy. J Infect Dis 160:891–895CrossRefPubMedGoogle Scholar
  20. 20.
    Panato APR, Tomasi LT, Simon CS, Madeira K, Simoes LR, Medeiros LR, Barichello T, Rosa MI (2014) Meta-analysis identifies tumor necrosis factor-alpha and interleukin-1 beta as diagnostic biomarkers for bacterial and aseptic meningitis. Curr Neurovasc Res 11:340–348CrossRefPubMedGoogle Scholar
  21. 21.
    Prasad R, Kapoor R, Srivastava R, Mishra OP, Singh TB (2014) Cerebrospinal fluid TNF-α, IL-6, and IL-8 in children with bacterial meningitis. Pediatr Neurol 50:60–65. CrossRefPubMedGoogle Scholar
  22. 22.
    Ramilo O, Sáez-Llorens X, Mertsola J, Jafari H, Olsen KD, Hansen EJ, Yoshinaga M, Ohkawara S, Nariuchi H, McCracken GH (1990) Tumor necrosis factor alpha/cachectin and interleukin 1 beta initiate meningeal inflammation. J Exp Med 172:497–507CrossRefPubMedGoogle Scholar
  23. 23.
    Sampedro MF, Patel R (2007) Infections associated with long-term prosthetic devices. Infect Dis Clin N Am 21:785–819. CrossRefGoogle Scholar
  24. 24.
    Scheithauer S, Bürgel U, Ryang Y-M, Haase G, Schiefer J, Koch S, Häfner H, Lemmen S (2009) Prospective surveillance of drain associated meningitis/ventriculitis in a neurosurgery and neurological intensive care unit. J Neurol Neurosurg Psychiatry 80:1381–1385. CrossRefPubMedGoogle Scholar
  25. 25.
    Schoenbaum SC, Gardner P, Shillito J (1975) Infections of cerebrospinal fluid shunts: epidemiology, clinical manifestations, and therapy. J Infect Dis 131:543–552CrossRefPubMedGoogle Scholar
  26. 26.
    Schuhmann MU, Ostrowski KR, Draper EJ, Chu J-W, Ham SD, Sood S, McAllister JP (2005) The value of C-reactive protein in the management of shunt infections. J Neurosurg 103:223–230. CrossRefPubMedGoogle Scholar
  27. 27.
    Srinivasan L, Kilpatrick L, Shah SS, Abbasi S, Harris MC (2016) Cerebrospinal fluid cytokines in the diagnosis of bacterial meningitis in infants. Pediatr Res 80:566–572. CrossRefPubMedGoogle Scholar
  28. 28.
    Sulik A, Kroten A, Wojtkowska M, Oldak E (2014) Increased levels of cytokines in cerebrospinal fluid of children with aseptic meningitis caused by mumps virus and echovirus 30. Scand J Immunol 79:68–72. CrossRefPubMedGoogle Scholar
  29. 29.
    Tabuchi S, Kadowaki M (2015) Neuroendoscopic surgery for ventriculitis and hydrocephalus after shunt infection and malfunction: preliminary report of a new strategy. Asian J Endosc Surg 8:180–184. CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Tang RB, Lee BH, Chung RL, Chen SJ, Wong TT (2001) Interleukin-1beta and tumor necrosis factor-alpha in cerebrospinal fluid of children with bacterial meningitis. Childs Nerv Syst 17:453–456CrossRefPubMedGoogle Scholar
  31. 31.
    Taskin E, Turgut M, Kilic M, Akbulut H, Aygun AD (2004) Serum procalcitonin and cerebrospinal fluid cytokines level in children with meningitis. Mediat Inflamm 13:269–273. CrossRefGoogle Scholar
  32. 32.
    Tunkel AR, Hasbun R, Bhimraj A, Byers K, Kaplan SL, Michael Scheld W, van de Beek D, Bleck TP, Garton HJL, Zunt JR (2017) 2017 Infectious Diseases Society of America’s clinical practice guidelines for healthcare-associated ventriculitis and meningitis. Clin Infect Dis 64:e34–e65. CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Vanaclocha V, Sáiz-Sapena N, Leiva J (1996) Shunt malfunction in relation to shunt infection. Acta Neurochir 138:829–834CrossRefPubMedGoogle Scholar
  34. 34.
    (2000) The management of neurosurgical patients with postoperative bacterial or aseptic meningitis or external ventricular drain-associated ventriculitis. Infection in Neurosurgery Working Party of the British Society for Antimicrobial Chemotherapy Br J Neurosurg 14:7–12Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of NeurosurgeryAdana City Training Research HospitalAdanaTurkey
  2. 2.Department of NeurosurgeryCukurova University of Medical SchoolAdanaTurkey
  3. 3.Pediatric Infectious Disease DepartmentCukurova University of Medical SchoolAdanaTurkey
  4. 4.Department of NeurosurgeryMedical Park HospitalGaziantepTurkey

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