RECOMBINANT SOLUBLE TUMOR-NECROSIS-FACTOR RECEPTOR PROTEINS PROTECT MICE FROM LIPOPOLYSACCHARIDE-INDUCED LETHALITY

被引:255
|
作者
LESSLAUER, W [1 ]
TABUCHI, H [1 ]
GENTZ, R [1 ]
BROCKHAUS, M [1 ]
SCHLAEGER, EJ [1 ]
GRAU, G [1 ]
PIGUET, PF [1 ]
POINTAIRE, P [1 ]
VASSALLI, P [1 ]
LOETSCHER, H [1 ]
机构
[1] UNIV GENEVA,CMU,DEPT PATHOL,CH-1211 GENEVA 4,SWITZERLAND
关键词
D O I
10.1002/eji.1830211134
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 in vivo efficacy of human recombinant soluble tumor necrosis factor (TNF) receptor protein to prevent and to treat lipopolysaccharide (LPS)-induced lethal toxicity in D-galactosamine-treated mice was investigated. Chimeric proteins of the receptor extracellular domains fused to the hinge region of human IgG3 were expressed in myeloma cells (rsTNFR-h-gamma-3). The fusion proteins had a disulfide-bonded dimeric structure. Upon intravenous injection, their serum concentration decreased relatively slowly after an initial phase of rapid elimination. D-galactosamine-sensitized mice were fully protected from the toxic effects of LPS, if the animal were pretreated with rsTNFR-h-gamma-3 at 20-mu-g/animal. Partial protection was seen at significantly lower doses and when rsTNFR-h-gamma-3 was given up to 3 h after LPS.
引用
收藏
页码:2883 / 2886
页数:4
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