This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hazelzet, J. A.
Right arrow Articles by Hack, C. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hazelzet, J. A.
Right arrow Articles by Hack, C. E.

 Previous Article  |  Next Article 

Infection and Immunity, November 1998, p. 5350-5356, Vol. 66, No. 11
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Complement Activation in Relation to Capillary Leakage in Children with Septic Shock and Purpura

Jan A. Hazelzet,1,* Ronald de Groot,2 Gerard van Mierlo,3 Koen F. M. Joosten,1 Edwin van der Voort,1 Anke Eerenberg,3 Marja H. Suur,2 Wim C. J. Hop,4 and C. Erik Hack3

Divisions of Pediatric Intensive Care,1 and Pediatric Infectious Diseases and Immunology,2 Department of Pediatrics, Sophia Children's Hospital/University Hospital Rotterdam, and Department of Biostatistics and Epidemiology, Erasmus University, Rotterdam,4 and Central Laboratory of The Netherlands Red Cross Blood Transfusion Services and Department of Internal Medicine, University Hospital VU, Amsterdam,3 The Netherlands

Received 30 March 1998/Returned for modification 17 June 1998/Accepted 24 August 1998

To assess the relationship between capillary leakage and inflammatory mediators during sepsis, blood samples were taken on hospital admission, as well as 24 and 72 h later, from 52 children (median age, 3.3 years) with severe meningococcal sepsis, of whom 38 survived and 14 died. Parameters related to cytokines (interleukin 6 [IL-6] IL-8, plasma phospholipase A2, and C-reactive protein [CRP]), to neutrophil degranulation (elastase and lactoferrin), to complement activation (C3a, C3b/c, C4b/c, and C3- and C4-CRP complexes), and to complement regulation (functional and inactivated C1 inhibitor and C4BP) were determined. The degree of capillary leakage was derived from the amount of plasma infused and the severity of disease by assessing the pediatric risk of mortality (PRISM) score. Levels of IL-6, IL-8, C3b/c, C3-CRP complexes, and C4BP on admission, adjusted for the duration of skin lesions, were significantly different in survivors and nonsurvivors (C3b/c levels were on average 2.2 times higher in nonsurvivors, and C3-CRP levels were 1.9 times higher in survivors). Mortality was independently related to the levels of C3b/c and C3-CRP complexes. In agreement with this, levels of complement activation products correlated well with the PRISM score or capillary leakage. Thus, these data show that complement activation in patients with severe meningococcal sepsis is associated with a poor outcome and a more severe disease course. Further studies should reveal whether complement activation may be a target for therapeutical intervention in this disease.

* Corresponding author. Mailing address: Division of Pediatric Intensive Care, Department of Pediatrics, Sophia Children's Hospital/University Hospital Rotterdam, P.O. Box 2060, 3000-CB Rotterdam, The Netherlands. Phone: (31) 104636363. Fax: (31) 104636796. E-mail: hazelzet{at}alkg.azr.nl.

Infection and Immunity, November 1998, p. 5350-5356, Vol. 66, No. 11
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Hellerud, B. C., Stenvik, J., Espevik, T., Lambris, J. D., Mollnes, T. E., Brandtzaeg, P. (2008). Stages of Meningococcal Sepsis Simulated In Vitro, with Emphasis on Complement and Toll-Like Receptor Activation. Infect. Immun. 76: 4183-4189 [Abstract] [Full Text]  
  • Schroth, M., Plank, C., Meissner, U., Eberle, K.-P., Weyand, M., Cesnjevar, R., Dotsch, J., Rascher, W. (2006). Hypertonic-Hyperoncotic Solutions Improve Cardiac Function in Children After Open-Heart Surgery. Pediatrics 118: e76-e84 [Abstract] [Full Text]  
  • Sprong, T., Roos, D., Weemaes, C., Neeleman, C., Geesing, C. L. M., Mollnes, T. E., van Deuren, M. (2006). Deficient alternative complement pathway activation due to factor D deficiency by 2 novel mutations in the complement factor D gene in a family with meningococcal infections. Blood 107: 4865-4870 [Abstract] [Full Text]  
  • Jarva, H., Ram, S., Vogel, U., Blom, A. M., Meri, S. (2005). Binding of the Complement Inhibitor C4bp to Serogroup B Neisseria meningitidis. J. Immunol. 174: 6299-6307 [Abstract] [Full Text]  
  • Sprong, T., Moller, A.-S. W., Bjerre, A., Wedege, E., Kierulf, P., van der Meer, J. W. M., Brandtzaeg, P., van Deuren, M., Mollnes, T. E. (2004). Complement Activation and Complement-Dependent Inflammation by Neisseria meningitidis Are Independent of Lipopolysaccharide. Infect. Immun. 72: 3344-3349 [Abstract] [Full Text]  
  • Sprong, T., Brandtzaeg, P., Fung, M., Pharo, A. M., Hoiby, E. A., Michaelsen, T. E., Aase, A., van der Meer, J. W. M., van Deuren, M., Mollnes, T. E. (2003). Inhibition of C5a-induced inflammation with preserved C5b-9-mediated bactericidal activity in a human whole blood model of meningococcal sepsis. Blood 102: 3702-3710 [Abstract] [Full Text]  
  • Zeerleder, S., Caliezi, C., van Mierlo, G., Eerenberg-Belmer, A., Sulzer, I., Hack, C. E., Wuillemin, W. A. (2003). Administration of C1 Inhibitor Reduces Neutrophil Activation in Patients with Sepsis. CVI 10: 529-535 [Abstract] [Full Text]  
  • Kvalsvig, A J, Unsworth, D J (2003). The immunopathogenesis of meningococcal disease. J. Clin. Pathol. 56: 417-422 [Abstract] [Full Text]  
  • Baines, P. B., Hart, C. A. (2003). Severe meningococcal disease in childhood. Br J Anaesth 90: 72-83 [Abstract] [Full Text]  
  • Bosch, I., Xhaja, K., Estevez, L., Raines, G., Melichar, H., Warke, R. V., Fournier, M. V., Ennis, F. A., Rothman, A. L. (2002). Increased Production of Interleukin-8 in Primary Human Monocytes and in Human Epithelial and Endothelial Cell Lines after Dengue Virus Challenge. J. Virol. 76: 5588-5597 [Abstract] [Full Text]  
  • Brandtzaeg, P., Bjerre, A., Ovstebo, R., Brusletto, B., Joo, G. B., Kierulf, P. (2001). Invited review: Neisseria meningitidis lipopolysaccharides in human pathology. Innate Immunity 7: 401-420 [Abstract]  
  • HACKETT, S.J., THOMSON, A.P. J., HART, C.A. (2001). Cytokines, chemokines and other effector molecules involved in meningococcal disease. J Med Microbiol 50: 847-859 [Abstract] [Full Text]  
  • van Deuren, M., Brandtzaeg, P., van der Meer, J. W. M. (2000). Update on Meningococcal Disease with Emphasis on Pathogenesis and Clinical Management. Clin. Microbiol. Rev. 13: 144-166 [Abstract] [Full Text]  
  • Schneider, D T, Nurnberger, W, Stannigel, H, Bonig, H, Gobel, U (1999). Adjuvant treatment of severe acute pancreatitis with C1 esterase inhibitor concentrate after haematopoietic stem cell transplantation. Gut 45: 733-736 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»