MONOCYTE CHEMOATTRACTANT PROTEIN-1 AND INTERLEUKIN-8 LEVELS IN URINE AND SERUM OF PATIENTS WITH HEMOLYTIC-UREMIC SYNDROME

The epidemic form of the hemolytic uremic syndrome (HUS) in children i s hallmarked by endothelial cell damage, most predominantly displayed by the glomerular capillaries. The influx of mononuclear (MO) and poly morphonuclear cells (PMNs) into the glomeruli may be an important even t in the initiation, prolongation, and progression of glomerular endot helial cell damage in HUS patients. The molecular mechanisms for the r ecruitment of these leukocytes into the kidney are unclear, but monocy te chemoattractant protein-1 (MCP-1) and IL-8 are suggested to be prim e candidates. In this study, we analyzed the presence of both chemokin es in 24-h urinary (n = 15) and serum (n = 14) samples of HUS children by specific ELISAs. Furthermore, kidney biopsies of three different H US children were examined for MO and PMN cell infiltration by histoche mical techniques and electron microscopy. Whereas the chemokines MCP-1 and IL-8 were present in only very limited amounts in urine of 17 nor mal control subjects, serial samples of HUS patients demonstrated sign ificantly elevated levels of both chemokines. HUS children with anuria showed higher initial and maximum chemokine levels than their counter parts without anuria. A strong positive correlation was observed betwe en urinary MCP-1 and IL-8 levels. Whereas initial serum IL-8 levels we re significantly increased in HUS children, serum MCP-1 levels were on ly slightly elevated compared with serum MCP-1 in control children. No correlation was found between urinary and serum chemokine concentrati ons. Histologic and EM studies of HUS biopsy specimens clearly showed the presence of MOs and to a lesser extent of PMNs in the glomeruli. T he present data suggest an important local role for MOs and PMNs in th e process of glomerular endothelial-cell damage. The chemokines MCP-1 and IL-8 may possibly be implicated in the pathogenesis of HUS through the recruitment and activation of MOs and PMNs, respectively.