COMBINED INHIBITION OF INTERLEUKIN-1 AND TUMOR-NECROSIS-FACTOR IN RODENT ENDOTOXEMIA - IMPROVED SURVIVAL AND ORGAN FUNCTION

被引：69

作者：

RUSSELL, DA ^{[1
]}

TUCKER, KK ^{[1
]}

CHINOOKOSWONG, N ^{[1
]}

THOMPSON, RC ^{[1
]}

KOHNO, T ^{[1
]}

机构：

[1] SYNERGEN INC,BOULDER,CO 80301

来源：

JOURNAL OF INFECTIOUS DISEASES | 1995年 / 171卷 / 06期

关键词：

D O I：

10.1093/infdis/171.6.1528

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The interleukin (IL)-1 receptor antagonist (Ra) and a polyethylene glycol-linked dimer of the type I soluble receptor of tumor necrosis factor (TNF), PEG-(rsTNF-RI)(2), were used to determine whether maximal protection against lethality and organ dysfunction is achieved by single or dual cytokine inhibition under rigorous conditions of rodent endotoxemia, inhibition of IL-l or TNF alone protected maximally against lethality when inhibitors were given simultaneously with lipopolysaccharide (LPS) under minimal lethal conditions. Combined inhibition of IL-1 and TNF was necessary to maximally protect against lethality when treatment was delayed until 7 h after LPS injection under minimal lethal conditions or when treatment was begun immediately after LPS injection under supralethal conditions. Improved survival in IL-1Ra- plus PEG-(rsTNF-RI)(2)-treated rats was associated with enhanced protection against renal and metabolic dysfunctions. Thus, under very severe conditions of endotoxemia, TNF and IL-1 may set independently to mediate lethality and some organ dysfunctions.

引用

页码：1528 / 1538

页数：11

共 28 条

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