COMPARISON OF A RECOMBINANT ENDOTOXIN-NEUTRALIZING PROTEIN WITH A HUMAN MONOCLONAL-ANTIBODY TO ENDOTOXIN FOR THE TREATMENT OF ESCHERICHIA-COLI SEPSIS IN RATS

被引:18
作者
KUPPERMANN, N
NELSON, DS
SALADINO, RA
THOMPSON, CM
SATTLER, F
NOVITSKY, TJ
FLEISHER, GR
SIBER, GR
机构
[1] HARVARD UNIV, SCH MED, DANA FARBER CANC INST, INFECT DIS LAB, BOSTON, MA 02115 USA
[2] CHILDRENS HOSP, DEPT MED, DIV EMERGENCY MED, BOSTON, MA 02115 USA
[3] ASSOCIATES CAPE COD INC, WOODS HOLE, MA USA
关键词
D O I
10.1093/infdis/170.3.630
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
A recombinant endotoxin-neutralizing protein (ENP) from Limulus polyphemus and a monoclonal IgM anti-lipid A antibody (HA-1A) were compared in a rat model of Escherichia coli sepsis. One hour after intraperitoneal challenge with 10(6) cfu of E. coli O18ac K1, animals were sensitized to endotoxin with lead acetate and treated with ENP, HA-1A, or saline, followed by ceftriaxone and gentamicin. Before treatment, 95% of rats had high-grade bacteremia and high serum endotoxin concentrations, which were similar in all treatment groups (P > .60). One hour after treatment, there was no bacterial growth in any blood sample, and endotoxin concentrations were significantly lower in the ENP group than in the HA-1A and saline groups (P < .01). At 24 h after challenge, survival in the ENP group was significantly higher than in the HA-1A saline group (P < .001). ENP improved survival in a rat model of E. coli sepsis with high mortality despite effective antibiotic therapy.
引用
收藏
页码:630 / 635
页数:6
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