Top

Intensive Care Medicine

Published in:

01-10-2005 | Pediatric Original

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

Authors: Enitan D. Carrol, Alistair P. J. Thomson, Ashley P. Jones, Graham Jeffers, C. Anthony Hart

Published in: Intensive Care Medicine | Issue 10/2005

Abstract

Objective

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.

Interventions

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%).

Conclusions

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.

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 172:433–439PubMed

Riordan FA, Marzouk O, Thomson AP, Sills JA, Hart CA (1996) Proinflammatory and anti-inflammatory cytokines in meningococcal disease. Arch Dis Child 75:453–454PubMed

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 89:4845–4849PubMed

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 169:157–161PubMed

Dissel JT van, van Langevelde P, Westendorp RG, Kwappenberg K, Frolich M (1998) Anti-inflammatory cytokine profile and mortality in febrile patients. Lancet 351:950–953PubMed

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 181:176–180CrossRefPubMed

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 10:1090–1095CrossRefPubMed

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 70:2187–2197CrossRefPubMed

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 190:2020–2030CrossRefPubMed

10.

Thomson AP, Sills JA, Hart CA (1991) Validation of the Glasgow Meningococcal Septicemia Prognostic Score: a 10-year retrospective survey. Crit Care Med 19:26–30PubMed

11.

Carcillo JA, Fields AI (2002) Clinical practice parameters for hemodynamic support of pediatric and neonatal patients in septic shock. Crit Care Med 30:1365–1378CrossRefPubMed

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 31:1250–1256CrossRefPubMed

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 167:471–475PubMed

14.

Sfeir T, Saha DC, Astiz M, Rackow EC (2001) Role of interleukin-10 in monocyte hyporesponsiveness associated with septic shock. Crit Care Med 29:129–133CrossRefPubMed

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 166:1475–1482CrossRefPubMed

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 30:2028–2037CrossRefPubMed

17.

Carrol ED, Thomson AP, Mobbs KJ, Hart CA (2000) The role of RANTES in meningococcal disease. J Infect Dis 182:363–366CrossRefPubMed

18.

Moller AS, Bjerre A, Brusletto B, Joo GB, Brandtzaeg P, Kierulf P (2005) Chemokine patterns in meningococcal disease. J Infect Dis 191:768–775CrossRefPubMed

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 363:203–209CrossRefPubMed

Title: A predominantly anti-inflammatory cytokine profile is associated with disease severity in meningococcal sepsis
Authors: Enitan D. Carrol
Alistair P. J. Thomson
Ashley P. Jones
Graham Jeffers
C. Anthony Hart
Publication date: 01-10-2005
Publisher: Springer-Verlag
Published in: Intensive Care Medicine / Issue 10/2005
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-005-2787-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Objective

Design and setting

Patients and participants

Interventions

Measurements and results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objective

Design and setting

Patients and participants

Interventions

Measurements and results

Conclusions

Please log in to get access to this content

Other articles of this Issue 10/2005

Are somatosensory evoked potentials the best predictor of outcome after severe brain injury?

What is the role of noninvasive ventilation in diastolic heart failure?

Some ICUs save more lifes than others: we need to know why!

Cortisol changes among patients with septic shock and the relationship to ICU and hospital stay

Are somatosensory evoked potentials the best predictor of outcome after severe brain injury? Caution in interpreting a systematic review

Reply to “Training in adult intensive care medicine in Spain”