大肠杆菌O157:H7相关溶血尿毒综合征患儿循环中的粒细胞集落刺激因子、C-X-C趋化因子和C-C趋化因子

Circulating granulocyte colony-stimulating factor, C-X-C, and C-C chemokines in children with Escherichia coli O157:H7 associated hemolytic uremic syndrome.

作者信息

Proulx François, Toledano Baruch, Phan Véronique, Clermont Marie-José, Mariscalco Michelle M, Seidman Ernest G

机构信息

Department of Pediatrics, Sainte-Justine Hospital, Montreal, Quebec, Canada.

出版信息

Pediatr Res. 2002 Dec;52(6):928-34. doi: 10.1203/00006450-200212000-00019.

DOI:10.1203/00006450-200212000-00019

PMID:12438672

Abstract

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.

摘要

白细胞与腹泻相关性溶血尿毒综合征（D(+) HUS）的发病机制有关。我们推测，粒细胞集落刺激因子（G-CSF）以及趋化因子上皮细胞来源的中性粒细胞激活蛋白-78（ENA-78）、生长相关癌基因-α（GRO-α）、巨噬细胞炎性蛋白-1β（MIP-1β）和单核细胞趋化蛋白-1（MCP-1）的循环水平升高与大肠杆菌O157:H7感染的疾病严重程度相关。我们比较了这些介质在大肠杆菌O157:H7肠炎、出血性结肠炎和溶血尿毒综合征病程中的循环浓度。我们的数据显示，入院时，溶血尿毒综合征患儿的G-CSF水平异常升高了10倍（p < 0.007），MIP-1β浓度升高了3倍（p < 0.001），而ENA-78值降低了2倍（p < 0.0001）。一周后，ENA-78浓度进一步下降了4倍（p < 0.0001），而MIP-1β水平恢复正常。需要腹膜透析的溶血尿毒综合征患者的G-CSF水平升高了6倍（p < 0.001），ENA-78水平降低了5倍（p < 0.001）。入院时，无并发症的O157:H7出血性结肠炎（HC）患儿的G-CSF（p < 0.001）和MIP-1β（p < 0.0001）浓度异常升高了3倍。那些患有O157:H7肠炎但无血便的患儿，其GRO-α、MIP-1β和MCP-1测量异常的发生率高于患有O157:H7 HC或溶血尿毒综合征的患儿：GRO-α（肠炎50%，HC 36%，溶血尿毒综合征17%；p < 0.06），MIP-1β（肠炎40%，HC 22%，溶血尿毒综合征11%；p < 0.02），MCP-1（肠炎77%，HC 20%，溶血尿毒综合征18%；p < 0.0001）。数据表明，无论是否发展为HC或溶血尿毒综合征，在大肠杆菌O157:H7肠炎期间都会产生GRO-α、MIP-1β和MCP-1。我们的数据表明，患有O157:H7相关溶血尿毒综合征的儿童可能出现G-CSF循环水平异常升高和ENA-78浓度降低。大肠杆菌O157:H7感染中白细胞募集的机制尚不清楚，有待进一步研究。