Circulating inflammatory cytokine levels in hemolytic uremic syndrome.
Experimental data suggest that the host's inflammatory response is involved in the pathophysiology of verotoxin-producing Escherichia coli (VTEC)-associated hemolytic uremic syndrome (HUS). We compared the circulating levels of pro- [interleukin (IL)-6, IL-8] and anti-inflammatory [IL-10 and IL-1 receptor antagonist (Ra)] mediators on enrollment among children with HUS due to E. coli O157:H7, according to the severity of renal dysfunction. The latter was evaluated by the occurrence of oligoanuria, the requirement for dialysis, and a glomerular filtration rate (GFR) </=80 ml/min per 1. 73 m(2) measured 1 year later. Increased levels of IL-6 (P<0.0001), IL-10 (P<0.0001), and IL-1Ra (P<0.07) were found among patients with HUS compared with normal controls. Children with severe renal dysfunction also had tenfold increased levels of IL-6 and higher concentrations of IL-10 and IL-1Ra. Both the IL-6/IL-10 (4.9+/-8.3 vs. 0.5+/-0.4, P=0.01) and the IL-6/IL-1Ra ratios (0.10+/-0.20 vs. 0. 01+/-0.01, P=0.04) were significantly increased. GFR correlated well with IL-6 levels, IL-6/IL-10 and IL-6/IL-1Ra ratios. Our data demonstrate that the inflammatory response of the host is associated with the severity of renal dysfunction during classic HUS. An imbalance between the pro- and the anti-inflammatory responses may be involved in the pathophysiology of VTEC-associated HUS.
Litalien
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C
Department of Pediatrics, Sainte-Justine Hospital, 3175 Chemin Côte Sainte-Catherine, Montréal, Québec, H3T-1C5, Canada.
Proulx
F
F
Mariscalco
M M
MM
Robitaille
P
P
Turgeon
J P
JP
Orrbine
E
E
Rowe
P C
PC
McLaine
P N
PN
Seidman
E
E
D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood*; D004926:Escherichia coli / Q000276:immunology*; D005260:Female; D005919:Glomerular Filtration Rate; D006463:Hemolytic-Uremic Syndrome / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000382:microbiology; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D017472:Receptors, Interleukin-1 / Q000819:agonists / Q000097:blood
D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D017472:Receptors, Interleukin-1; D016753:Interleukin-10