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Clinical and Diagnostic Laboratory Immunology, November 2003, p. 1090-1095, Vol. 10, No. 6
1071-412X/03/$08.00+0     DOI: 10.1128/CDLI.10.6.1090-1095.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Characterization of the Cytokine Immune Response in Children Who Have Experienced an Episode of Typical Hemolytic-Uremic Syndrome

Children's Hospital and Department of Pediatric Nephrology of the Technical University of Munich, 80804 Munich,¹ Department of Medical Immunology, Charité, Humboldt-University, 10098 Berlin,² Department of Biochemical Pharmacology, University of Konstanz, 78464 Konstanz, Germany³

Received 19 June 2002/ Returned for modification 18 September 2002/ Accepted 4 August 2003

The lipopolysaccharide (LPS) of enterohemorrhagic Escherichia coli (EHEC) and Shiga toxin together substantially contribute to the pathophysiology of typical hemolytic-uremic syndrome (HUS). Both factors have been shown to be immune stimulators and could play a key role in the individual innate immune response, characterized by proinflammatory and anti-inflammatory cytokines. By use of a whole blood stimulation model, we therefore compared the LPS- and superantigen-induced cytokine responses in children who had been having recovering from an acute episode of typical HUS for at least 6 months (group 1) with those in controls, who consisted of patients seen in the pediatric neurology outpatient department for routine examination (group 2). Samples were analyzed for cytokine protein levels and the levels of mRNA production. LPS stimulation revealed lower levels of interleukin 10 (IL-10) (P < 0.05) and increased levels of gamma interferon (P < 0.05) and increased ratios of pro- and anti-inflammatory cytokines (P < 0.05 for the IL-1ß/IL-10 ratio; P < 0.05 for the tumor necrosis factor alpha/IL-10 ratio) in group 1. In addition superantigen stimulation showed decreased IL-2 levels in group 1 (P < 0.01). Our results suggest an alteration of the cytokine response characterized by high proinflammatory cytokine levels and low anti-inflammatory cytokine levels as well as low levels of IL-2 production in children who have experienced an episode of typical HUS. We hypothesize that this altered immune response is not a residual effect of the infection but a preexisting characteristic of the patient. This could be one reason why individuals infected with EHEC are potentially predisposed to a systemic disease (HUS).