Exacerbation of toxic effects by endotoxin contamination of recombinant human tumor necrosis factor View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1989-07

AUTHORS

Yukio Ozaki, Toshio Oyama, Shoji Kume

ABSTRACT

The toxic effects of endotoxin-free human recombinant tumor necrosis factor (rH-TNF), shown to contain <50 pg endotoxin/mg rH-TNF and endotoxin coadministered at 4–400 ng endotoxin/mg rH-TNF in female Sprague-Dawley rats. The mean lethal dose of 5.9 mg/kg rH-TNF found for the endotoxin-free rH-TNF was far higher than that attributed to rH-TNF by other investigators. Coadministration with endotoxin derived from E. Coli. Salmonella abortus equi, or Serratia marcescens reduced the apparent mean lethal dose of rH-TNF in correspondence to the endotoxin concentration, with a value of 0.7 mg/kg rH-TNF observed at 1600 ng, 757 ng, and 5260 ng endotoxin/mg rH-TNF, respectively. Coadministration also resulted in more severe histopathologic and physicochemical effects than rH-TNF alone. Histopathologic abnormalities observed only in coadministration included interlobular edema and hemorrhage of the pancreas and, most remarkably, splenomegaly, which was not observed with rH-TNF alone even at lethal doses. The results indicate that particular care in determining endotoxin contamination is essential in any consideration of TNF toxicity. More... »

PAGES

231-237

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/bf00451647

DOI

http://dx.doi.org/10.1007/bf00451647

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1046498079

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/2522355


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