Intensive Care Medicine

, Volume 31, Issue 10, pp 1415–1419 | Cite as

A predominantly anti-inflammatory cytokine profile is associated with disease severity in meningococcal sepsis

  • Enitan D. Carrol
  • Alistair P. J. Thomson
  • Ashley P. Jones
  • Graham Jeffers
  • C. Anthony Hart
Pediatric Original



This study aimed to determine whether an anti-inflammatory profile in meningococcal disease is associated with an increased risk of severe disease or septic shock.

Design and setting

Prospective observational study in a tertiary care children’s hospital.

Patients and participants

63 children with confirmed meningococcal disease.


Plasma concentrations of interleukin-1 receptor antagonist (IL-1Ra), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-α (TNF) were assayed on admission. Receiver operator characteristic curve analysis was used to determine optimum thresholds for IL-1Ra:TNF, IL-1Ra:IL-6 and IL-1Ra:IL-8 ratios.

Measurements and results

Median IL-1Ra:TNF and IL-1Ra:IL-6 ratios were significantly higher in severe disease with septic shock than in severe disease without septic shock and in non severe disease (IL-1Ra:TNF 263 vs. 185 vs. 108; IL-1Ra:IL-6 139 vs. 23 vs. 17). Median IL-1Ra:IL-8 ratios were not significantly different in the three groups. A significantly larger proportion of children with high IL-1Ra:TNF-α and IL-1Ra:IL-6 ratios developed severe disease with septic shock than those with a low ratios (95.2% vs. 4.8%; 76.2% vs. 23.8%).


An anti-inflammatory profile appears to be associated with the development of severe disease and septic shock in meningococcal sepsis. This may imply that experimental new therapies of pro-inflammatory cytokine inhibition and anti-inflammatory cytokines in meningococcal disease could be detrimental.


Meningococcal disease Cytokine Septic shock Logistic regression 


  1. 1.
    Deuren M van, van der Ven-Jongekrijg J, Bartelink AK, van Dalen R, Sauerwein RW, van der Meer JW (1995) Correlation between proinflammatory cytokines and antiinflammatory mediators and the severity of disease in meningococcal infections. J Infect Dis 172:433–439PubMedGoogle Scholar
  2. 2.
    Riordan FA, Marzouk O, Thomson AP, Sills JA, Hart CA (1996) Proinflammatory and anti-inflammatory cytokines in meningococcal disease. Arch Dis Child 75:453–454PubMedGoogle Scholar
  3. 3.
    Van Zee KJ, Kohno T, Fischer E, Rock CS, Moldawer LL, Lowry SF (1992) Tumor necrosis factor soluble receptors circulate during experimental and clinical inflammation and can protect against excessive tumor necrosis factor alpha in vitro and in vivo. Proc Natl Acad Sci U S A 89:4845–4849PubMedGoogle Scholar
  4. 4.
    Deuren M van, van der Ven-Jongekrijg J, Demacker PN, Bartelink AK, van Dalen R, Sauerwein RW, Gallati H, Vannice JL, van der Meer JW (1994) Differential expression of proinflammatory cytokines and their inhibitors during the course of meningococcal infections. J Infect Dis 169:157–161PubMedGoogle Scholar
  5. 5.
    Dissel JT van, van Langevelde P, Westendorp RG, Kwappenberg K, Frolich M (1998) Anti-inflammatory cytokine profile and mortality in febrile patients. Lancet 351:950–953PubMedGoogle Scholar
  6. 6.
    Gogos CA, Drosou E, Bassaris HP, Skoutelis A (2000) Pro- versus anti-inflammatory cytokine profile in patients with severe sepsis: a marker for prognosis and future therapeutic options. J Infect Dis 181:176–180CrossRefPubMedGoogle Scholar
  7. 7.
    Westerholt S, Pieper AK, Griebel M, Volk HD, Hartung T, Oberhoffer R (2003) Characterization of the cytokine immune response in children who have experienced an episode of typical hemolytic-uremic syndrome. Clin Diagn Lab Immunol 10:1090–1095CrossRefPubMedGoogle Scholar
  8. 8.
    Thakur A, Xue M, Stapleton F, Lloyd AR, Wakefield D, Willcox MD (2002) Balance of pro- and anti-inflammatory cytokines correlates with outcome of acute experimental Pseudomonas aeruginosa keratitis. Infect Immun 70:2187–2197CrossRefPubMedGoogle Scholar
  9. 9.
    Wamachi AN, Mayadev JS, Mungai PL, Magak PL, Ouma JH, Magambo JK, Muchiri EM, Koech DK, King CH, King CL (2004) Increased ratio of tumor necrosis factor-alpha to interleukin-10 production is associated with Schistosoma haematobium-induced urinary-tract morbidity. J Infect Dis 190:2020–2030CrossRefPubMedGoogle Scholar
  10. 10.
    Thomson AP, Sills JA, Hart CA (1991) Validation of the Glasgow Meningococcal Septicemia Prognostic Score: a 10-year retrospective survey. Crit Care Med 19:26–30PubMedGoogle Scholar
  11. 11.
    Carcillo JA, Fields AI (2002) Clinical practice parameters for hemodynamic support of pediatric and neonatal patients in septic shock. Crit Care Med 30:1365–1378CrossRefPubMedGoogle Scholar
  12. 12.
    Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G (2003) 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 31:1250–1256CrossRefPubMedGoogle Scholar
  13. 13.
    Halstensen A, Ceska M, Brandtzaeg P, Redl H, Naess A, Waage A (1993) Interleukin-8 in serum and cerebrospinal fluid from patients with meningococcal disease. J Infect Dis 167:471–475PubMedGoogle Scholar
  14. 14.
    Sfeir T, Saha DC, Astiz M, Rackow EC (2001) Role of interleukin-10 in monocyte hyporesponsiveness associated with septic shock. Crit Care Med 29:129–133CrossRefPubMedGoogle Scholar
  15. 15.
    Fumeaux T, Pugin J (2002) Role of interleukin-10 in the intracellular sequestration of human leukocyte antigen-DR in monocytes during septic shock. Am J Respir Crit Care Med 166:1475–1482CrossRefPubMedGoogle Scholar
  16. 16.
    Fumeaux T, Dufour J, Stern S, Pugin J (2004) Immune monitoring of patients with septic shock by measurement of intraleukocyte cytokines. Intensive Care Med 30:2028–2037CrossRefPubMedGoogle Scholar
  17. 17.
    Carrol ED, Thomson AP, Mobbs KJ, Hart CA (2000) The role of RANTES in meningococcal disease. J Infect Dis 182:363–366CrossRefPubMedGoogle Scholar
  18. 18.
    Moller AS, Bjerre A, Brusletto B, Joo GB, Brandtzaeg P, Kierulf P (2005) Chemokine patterns in meningococcal disease. J Infect Dis 191:768–775CrossRefPubMedGoogle Scholar
  19. 19.
    Pathan N, Hemingway CA, Alizadeh AA, Stephens AC, Boldrick JC, Oragui EE, McCabe C, Welch SB, Whitney A, O’Gara P, Nadel S, Relman DA, Harding SE, Levin M (2004) Role of interleukin 6 in myocardial dysfunction of meningococcal septic shock. Lancet 363:203–209CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Enitan D. Carrol
    • 1
    • 2
    • 3
  • Alistair P. J. Thomson
    • 2
    • 3
  • Ashley P. Jones
    • 2
    • 4
  • Graham Jeffers
    • 2
  • C. Anthony Hart
    • 3
  1. 1.Wellcome Trust Research LaboratoriesChichiriMalawi
  2. 2.Institute of Child HealthRLCH NHS Trust, Alder HeyLiverpoolUK
  3. 3.Department of Medical MicrobiologyUniversity of LiverpoolLiverpoolUK
  4. 4.Centre for Medical Statistics and Health Evaluation, School Of Health SciencesUniversity of LiverpoolLiverpoolUK

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