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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.


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