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Cerebrospinal fluid levels of interleukin-6 and interleukin-12 in children with meningitis

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Abstract

Purpose

Certain cytokines play important roles in the pathophysiology of meningitis. The main purpose of this study was to investigate if the levels of interleukin-6 (IL-6) and interleukin-12 (IL-12) in cerebrospinal fluid (CSF) could be diagnostic predictors of bacterial meningitis in children.

Methods

CSF was obtained from 95 patients suspected with meningitis. These cases were classified to the bacterial meningitis (n = 12), aseptic meningitis (n = 41), and nonmeningitis (n = 42) groups. The levels of IL-6 and IL-12 in CSF were measured using the enzyme-linked immmunosorbent assays test.

Results

The CSF IL-6 levels in the bacterial meningitis group (45.2 ± 50.0 pg/ml) were significantly higher than those in the aseptic meningitis group (12.9 ± 10.2 pg/ml) and the nonmeningitis group (6.5 ± 7.8 pg/ml; p < 0.05). The CSF IL-12 levels in the bacterial meningitis group (69.8 ± 67.1 pg/ml) were significantly higher than those in the aseptic meningitis group (22.9 ± 10.8 pg/ml) and the nonmeningitis group (15.3 ± 11.2 pg/ml; p < 0.05). With regard to diagnosis, the measurement of CSF IL-6 and IL-12 levels showed sensitivities of 96% and 96%, respectively, and specificities of 51% and 75%, respectively.

Conclusion

It is suggested that the CSF IL-6 and IL-12 levels are useful markers for distinguishing bacterial meningitis from aseptic meningitis.

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References

  1. Kilpi T, Anttila M, Kallio MJ, Peltola H (1991) Severity of childhood bacterial meningitis and duration of illness before diagnosis. Lancet 338:406–409

    Article  CAS  PubMed  Google Scholar 

  2. McCracken GH, Mustafa MM, Ramilo O, Olsen KD, Risser RC (1989) Cerebrospinal fluid interleukin 1-beta and tumor necrosis factor concentrations and outcome from neonatal gram-negative enteric bacillary meningitis. Pediatr Infect Dis 8:155–159

    Google Scholar 

  3. Buke C, Bundschu J, Gallati H, Bartmann P, Pohlandt F (1994) Interleukin-6: a sensitive parameter for the early diagnosis of neonatal bacterial infection. Pediatrics 93:54–58

    Google Scholar 

  4. Okusawa S, Gelfand JA, Ikejima T (1988) Interleukin-1 induces a shock-like state in rabbits: synergism with tumor necorsis factor and the effect of cyclooxygenase inhibitiors. J Clin Invest 81:1162–1172

    Article  CAS  PubMed  Google Scholar 

  5. Harris MC, Costarino AT Jr, Sullivan JS, Dulkerian S, McCawley L, Corcoran L, Butler S, Kilpatrick L (1994) Cytokine elevations in critically ill infants with sepsis and necrotizing enterocolitis. J Pediatr 124:105–111

    Article  CAS  PubMed  Google Scholar 

  6. Helminen M, Vesikari T (1987) Spontaneous and inducible interleukin 1 production from peripheral blood monocytes in bacterial and viral infections in children. Pediatr Infect Dis 6:1102–1106

    CAS  Google Scholar 

  7. Waage A, Espevik T (1988) Interleukin-1 potentiates the lethal effect of tumor necrosis factor α/cachectin in mice. J Exp Med 167:1987–1992

    Article  CAS  PubMed  Google Scholar 

  8. Chonmaitree T, Baron S (1991) Bacteria and viruses induce production of interferon in the cerebrospinal fluid of children with acute meningitis: a study of 57 cases and review. Rev Infect Dis 13:106–115

    Google Scholar 

  9. Mastroianni CM, Paoletti F, Rivosecchi RM, Lancella L, Ticca F, Vullo V, Delia S (1994) Cerebrospinal fluid interleukin-8 in children with purulent bacterial and tuberculous meningitis. Pediatr Infect Dis 13:1008–1010

    CAS  Google Scholar 

  10. Mustafa MM, Lebel MH, Ramilo O, Olsen KD, Reisch JS, Beutler B, McCracken GH Jr (1989) Correlation of interleukin-1β and cachectin concentrations in cerebrospinal fluid and outcome from bacterial meningitis. J Pediatr 15:208–213

    Google Scholar 

  11. Nadal D, leppert D, Frei K, Gallo P, Lamche H, Fontana A (1989) Tumour necrosis factor-α in infectious meningitis. Arch Dis Child 64:1274–1279

    Article  CAS  PubMed  Google Scholar 

  12. Tsai ML, Chen WC, Wang YC, Hung KL (1996) Cerebrospinal fluid interleukin-6, interleukin-8 and tumor necrosis factor-α in children with central nervous infections. Acta Ped Sin 37:16–21

    CAS  Google Scholar 

  13. Tang RB, Lee BH, Chung RL, Chen SJ, Wong TT (2001) Interelukin 1β and tumor necrosis factor-α in cerebrospinal fluid of children with bacterial meningitis. Childs Nerv Syst 17:453–456

    Article  CAS  PubMed  Google Scholar 

  14. Kishimoto T (1989) The biology of interleukin-6. Blood 74:1–10

    CAS  PubMed  Google Scholar 

  15. Saladino R, Erikson M, Levy N, Bachman D, Siber GR, Fleisher GR (1992) Utility of serum interleukin-6 for diagnosis of invasive bacterial disease in children. Ann Emerg Med 21:1413–1417

    Article  CAS  PubMed  Google Scholar 

  16. Rusconi F, Parizzi F, Garlaschi L, Assael BM, Sironi M, Ghezzi P, Mantovani A (1991) Interleukin 6 activity in infants and children with bacterial meningitis. Pediatr Infect Dis 10:117–121

    Article  CAS  Google Scholar 

  17. Torre D, Zeroli C, Ferraro G, Speranza F, Tambini R, Martegani R, Fiori GP (1992) Cerebrospinal fluid levels of IL-6 in patients with acute infections of the central nervous system. Scand J Infect Dis 24:787–791

    Article  CAS  PubMed  Google Scholar 

  18. Gendrel D, Raymond J, Coste J, Moulin F, Lorrot M, Guerin S, Ravilly S, Lefevre H, Royer C, Lacombe C, Palmer P, Bohuon C (1999) Comparison of procalcitonin with C-reactive protein, interleukin 6 and interferon-alpha for differentiation of bacterial vs. viral infections. Pediatr Infect Dis 18:875–881

    Article  CAS  Google Scholar 

  19. Sheldon J, Riches P, Gooding R, Soni N, Hobbs JR (1993) C-reactive protein and its cytokine mediators in intensive-care patients. Clin Chem 39:147–50

    CAS  PubMed  Google Scholar 

  20. Stearman M, Southgate HJ (1994) The use of cytokine and C-reactive protein measurements in cerebrospinal fluid during acute infective meningitis. Ann Clin Biochem 31:255–261

    CAS  PubMed  Google Scholar 

  21. Tatara R, Imai H (2000) Serum C-reactive protein in the differential diagnosis of childhood meningitis. Pediatr Int 42:541–546

    Article  CAS  PubMed  Google Scholar 

  22. Hashim IA, Walsh A, Hart A, Hart CA, Shenkin A (1995) Cerebrospinal fluid interleukin-6 and its diagnostic value in the investigation of meningitis. Ann Clin Biochem 32:289–296

    PubMed  Google Scholar 

  23. Kanoh Y, Ohtani H (1997) Levels of interleukin-6, CRP and alpha 2 macroglobulin in cerebrospinal fluid and serum as indicator of blood-CSF barrier damage. Biochem Mol Biol Int 43:269–278

    CAS  PubMed  Google Scholar 

  24. Kornelisse RF, Hack CE, Savelkoul HF, van der Pouw Kraan TC, Hop WC, van Mierlo G, Suur MH, Neijens HJ, de Groot R (1997) Intrathecal production of interleukin-12 and gamma interferon in patients with bacterial meningitis. Infect Immun 65:877–881

    CAS  PubMed  Google Scholar 

  25. Tauber MG, Moser B (1999) Cytokines and chemokines in meningeal inflammation: biology and clinical implications. Clin Infect Dis 28:1–12

    Article  CAS  PubMed  Google Scholar 

  26. Tang RB, Chen SJ, Wu KK, Lee BH, Chen PY (1997) Interferon γ in cerebrospinal fluid of children with aseptic meningitis. J Chin Med Assoc 59:248–253

    CAS  Google Scholar 

  27. Azuma H, Tsuda N, Sasaki K, Okuno A (1997) Clinical significance of cytokine measurement for detection of meningitis. J Pediatr 131:463–465

    Article  CAS  PubMed  Google Scholar 

  28. Sundgren-Andersson AK, Ostlund P, Bartfai T (1998) IL-6 is essential in TNF-alpha-induced fever. Am J Physiol 275:2028–2034

    Google Scholar 

  29. Dulkerian SJ, Kilpatrick L, Costarino AT Jr, McCawley L, Fein J, Corcoran L, Zirin S, Harris MC (1995) Cytokine elevations in infants with bacterial and aseptic meningitis. J Pediatr 126:872–876

    Article  CAS  PubMed  Google Scholar 

  30. Chavanet P, Bonnotte B, Guiguet M, Zeller V, Solary E, Maurice L, Casasnovas O, Caillot D, Waldner A, Kisterman JP et al (1992) High concentrations of intrathecal interleukin-6 in human bacterial and nonbacterial meningitis. J Infect Dis 166:428–431

    CAS  PubMed  Google Scholar 

  31. 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 28:215–219

    Article  PubMed  Google Scholar 

  32. Rea IM, McNerlan SE, Alexander HD (2000) Total serum IL-12 and IL-12p40, but not IL-12p70, are increased in the serum of older subjects; relationship to CD3(+) and NK subsets. Cytokine 12:156–159

    Article  CAS  PubMed  Google Scholar 

  33. Stahel PF, Kossmann T, Joller H, Trentz O, Morganti-Kossmann MC (1998) Increased interleukin-12 levels in human cerebrospinal fluid following severe head trauma. Neurosci Lett 249:123–126

    Article  CAS  PubMed  Google Scholar 

  34. Mastroianni CM, Paoletti F, Lichtner M, D'Agostino C, Vullo V, Delia S (1997) Cerebrospinal fluid cytokines in patients with tuberculous meningitis. Clin Immunol Immunopathol 84:171–176

    Article  CAS  PubMed  Google Scholar 

  35. Turrin NP, Rivest S (2004) Innate immune reaction in response to seizures: implications for the neuropathology associated with epilepsy. Neurobiol Dis 16:321–334

    Article  CAS  PubMed  Google Scholar 

  36. Hazelzet JA, Kornelisse RF, van der Pouw Kraan TC, Joosten KF, van der Voort E, van Mierlo G, Suur MH, Hop WC, de Groot R, Hack CE (1997) Interleukin 12 levels during the initial phase of septic shock with purpura in children: relation to severity of disease. Cytokine 9:711–716

    Article  CAS  PubMed  Google Scholar 

  37. Bidarkundi GK, Wig JD, Bhatnagar A, Majumdar S (2002) Clinical relevance of intracellular cytokines IL-6 and IL-12 in acute pancreatitis, and correlation with APACHE III score. Brit J Biomed Sci 59:85–89

    CAS  Google Scholar 

  38. Leal IS, Smedegard B, Andersen P, Appelberg R (1999) Interleukin-6 and interleukin-12 participate in induction of a type 1 protective T-cell response during vaccination with a tuberculosis subunit vaccine. Infect Immun 67:5747–5754

    CAS  PubMed  Google Scholar 

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Acknowledgment

The study was supported by grants from the Taipei Veterans General Hospital.

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Authors and Affiliations

  1. Department of Pediatrics, Taipei Veterans General Hospital, 201, Sec. 2, Shih-Pai Road, Taipei, Taiwan, Republic of China

    Chia-Chang Hsieh, Jen-Her Lu, Shu-Jen Chen, Cheng-Chou Lan, Wen-Chi Chow & Ren-Bin Tang

  2. National Yang-Ming University, Taipei, Taiwan, Republic of China

    Chia-Chang Hsieh, Jen-Her Lu, Shu-Jen Chen, Cheng-Chou Lan, Wen-Chi Chow & Ren-Bin Tang

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  1. Chia-Chang Hsieh
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Correspondence to Ren-Bin Tang.

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Hsieh, CC., Lu, JH., Chen, SJ. et al. Cerebrospinal fluid levels of interleukin-6 and interleukin-12 in children with meningitis. Childs Nerv Syst 25, 461–465 (2009). https://doi.org/10.1007/s00381-008-0715-4

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  • DOI: https://doi.org/10.1007/s00381-008-0715-4

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