Circulating granulocyte colony-stimulating factor, C-X-C, and C-C chemokines in children with Escherichia coli O157:H7 associated hemolytic uremic syndrome.
Leukocytes are implicated in the pathogenesis of diarrhea-associated hemolytic uremic syndrome (D(+) HUS). We hypothesized that increased circulating levels of granulocyte colony-stimulating factor (G-CSF), and the chemokines epithelial cell-derived neutrophil-activating protein-78 (ENA-78), growth related oncogen-alpha (GRO-alpha), macrophage inflammatory protein-1beta (MIP-1beta), and monocyte chemotactic protein-1 (MCP-1) are related to the severity of illness in Escherichia coli O157:H7 infections. We compared the circulating concentrations of these mediators in the course of E. coli O157:H7 enteritis, hemorrhagic colitis, and HUS. Our data show that, on admission, children with HUS presented 10-fold abnormally increased levels of G-CSF (p < 0.007), 3-fold increased MIP-1beta concentrations (p < 0.001), and 2-fold lower values of ENA-78 (p < 0.0001). One week later, a further 4-fold decrease in ENA-78 concentration was noted (p < 0.0001) whereas MIP-1beta levels returned to normal. HUS patients requiring peritoneal dialysis showed 6-fold increased G-CSF (p < 0.001) and 5-fold decreased ENA-78 (p < 0.001) levels. On admission, children with uncomplicated O157:H7 hemorrhagic colitis (HC) presented 3-fold abnormally increased concentrations of G-CSF (p < 0.001) and MIP-1beta (p < 0.0001). Those with O157:H7 enteritis but no bloody stools showed higher rates of abnormal GRO-alpha, MIP-1beta, and MCP-1 measurements than children with O157:H7 HC or HUS: GRO-alpha (50% enteritis, 36% HC, 17% HUS; p < 0.06), MIP-1beta (40% enteritis, 22% HC, 11% HUS; p < 0.02), MCP-1 (77% enteritis, 20% HC, 18% HUS; p < 0.0001). The data indicates that GRO-alpha, MIP-1beta, and MCP-1 are produced during E. coli O157:H7 enteritis, whether or not HC or HUS develops. Our data suggest that children with O157:H7 associated HUS may present abnormally increased circulating levels of G-CSF and decreased ENA-78 concentrations. The mechanisms responsible for leukocytes recruitment in O157:H7 infections are unclear and await further studies.
Proulx
François
F
Department of Pediatrics, Sainte-Justine Hospital, Montreal, Quebec, Canada. fproulx_01@yahoo.ca
Toledano
Baruch
B
Phan
Véronique
V
Clermont
Marie-José
MJ
Mariscalco
Michelle M
MM
Seidman
Ernest G
EG
D000293:Adolescent; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000097:blood; D054407:Chemokine CCL4; D054360:Chemokine CXCL1; D054365:Chemokine CXCL5; D018925:Chemokines / Q000097:blood; D019742:Chemokines, CC / Q000097:blood*; D019743:Chemokines, CXC / Q000097:blood*; D002630:Chemotactic Factors / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003092:Colitis / Q000097:blood / Q000150:complications / Q000276:immunology; D004751:Enteritis / Q000097:blood / Q000150:complications / Q000276:immunology; D004927:Escherichia coli Infections / Q000097:blood* / Q000150:complications / Q000276:immunology*; D019453:Escherichia coli O157; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood*; D006463:Hemolytic-Uremic Syndrome / Q000097:blood* / Q000209:etiology / Q000276:immunology* / Q000628:therapy; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D016209:Interleukin-8 / Q000031:analogs & derivatives* / Q000097:blood; D019402:Macrophage Inflammatory Proteins / Q000097:blood; D008297:Male; D010530:Peritoneal Dialysis
C475829:CXCL1 protein, human; C486263:CXCL5 protein, human; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D054360:Chemokine CXCL1; D054365:Chemokine CXCL5; D018925:Chemokines; D019742:Chemokines, CC; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins; D016179:Granulocyte Colony-Stimulating Factor