Recombinant soluble tumor necrosis factor receptor proteins protect mice from lipopolysaccharide‐induced lethality

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Abstract
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-hγ3). 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-hγ3 at 20 μg/animal. Partial protection was seen at significantly lower doses and when rsTNFR-hγ3 was given up to 3 h after LPS.