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)-asso ciated hemolytic uremic syndrome (HUS). We compared the circulating levels of pro- [interleukin (IL)-6, IL-8] and anti-inflammatory [IL-10 and IL-1 re ceptor antagonist (Ra)] mediators on enrollment among children with HUS due to E. coli O157:H7, according to the severity of renal dysfunction. The la tter was evaluated by the occurrence of oligoanuria, the requirement for di alysis, and a glomerular filtration rate (GFR) less than or equal to 80 mi/ min per 1.73 m(2) measured 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 c ompared with normal controls. Children with severe renal dysfunction also h ad 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 incr eased. GFR correlated well with IL-6 levels, IL-6/IL-10 and IL-6/IL-1Ra rat ios. Our data demonstrate that the inflammatory response of the host is ass ociated with the severity of renal dysfunction during classic HUS. An imbal ance between the pro- and the anti-inflammatory responses may be involved i n the pathophysiology of VTEC-associated HUS.