Increased serum IL-10 and endothelin levels in hemolytic uremic syndrome caused by Escherichia coli O157.
BACKGROUND
Shiga toxin, produced by Escherichia coli O157:H7, is important for the pathogenicity of the epidemic form of hemolytic uremic syndrome (HUS). This toxin has recently been found to stimulate endothelin-1 synthesis in cultured endothelial cells in vitro.


METHODS
We investigated endothelin and cytokine levels in sera during a large outbreak of E. coli O157:H7 infection in Osaka, Japan, in 1996. Eleven patients with HUS and 9 patients with hemorrhagic colitis at the onset of E. coli O157:H7 infection were studied.


RESULTS
Serum IL-6 (p < 0.01), IL-8 (p < 0.05), IL-10 (p < 0.001) and endothelin (p < 0.001) levels were significantly increased in patients with HUS compared to those with colitis only. The serum thrombomodulin level, a molecular marker of endothelial damage, also showed a significant positive correlation with serum IL-6 (p < 0.01), IL-8 (p < 0.01), IL-10 (p < 0.01) and endothelin (p < 0.001) levels. In a HUS patient, the increase in serum IL-10 and endothelin levels reached a plateau prior to the peak of serum creatinine levels.


CONCLUSIONS
Increased serum endothelin synthesis by Shiga toxin in vivo was proven in HUS secondary to E. coli O157:H7 infection. Increased serum endothelin and IL-10 levels were speculated to be associated with the development of HUS through vascular endothelial damage caused by E. coli O157:H7 infection.
Yamamoto
T
T
Department of Pediatrics, Faculty of Medicine, Osaka University, Osaka, Japan.
Nagayama
K
K
Satomura
K
K
Honda
T
T
Okada
S
S
D016022:Case-Control Studies; D003092:Colitis / Q000097:blood / Q000453:epidemiology / Q000209:etiology; D003404:Creatinine / Q000097:blood; D004196:Disease Outbreaks; D019332:Endothelin-1 / Q000097:blood*; D004927:Escherichia coli Infections / Q000097:blood* / Q000453:epidemiology / Q000209:etiology*; D019453:Escherichia coli O157 / Q000472:pathogenicity*; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000097:blood / Q000453:epidemiology / Q000209:etiology; D006463:Hemolytic-Uremic Syndrome / Q000097:blood* / Q000453:epidemiology / Q000209:etiology*; D006801:Humans; D016753:Interleukin-10 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D007564:Japan / Q000453:epidemiology; D008297:Male; D018180:Thrombomodulin / Q000097:blood; D013997:Time Factors
D019332:Endothelin-1; D015850:Interleukin-6; D016209:Interleukin-8; D018180:Thrombomodulin; D016753:Interleukin-10; D003404:Creatinine