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

Eur J Immunol. 1991 Nov;21(11):2883-6. doi: 10.1002/eji.1830211134.


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 micrograms/animal. Partial protection was seen at significantly lower doses and when rsTNFR-h gamma 3 was given up to 3 h after LPS.

MeSH terms

  • Animals
  • Endotoxins / antagonists & inhibitors*
  • Immunoglobulin G / genetics
  • Lipopolysaccharides / toxicity*
  • Mice
  • Receptors, Cell Surface* / chemistry
  • Receptors, Cell Surface* / genetics
  • Receptors, Tumor Necrosis Factor
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / pharmacokinetics
  • Recombinant Fusion Proteins / pharmacology
  • Shock, Septic / prevention & control*
  • Solubility
  • Tumor Necrosis Factor-alpha


  • Endotoxins
  • Immunoglobulin G
  • Lipopolysaccharides
  • Receptors, Cell Surface
  • Receptors, Tumor Necrosis Factor
  • Recombinant Fusion Proteins
  • Tumor Necrosis Factor-alpha