Tumor necrosis factor alone does not explain the lethal effect of lipopolysaccharide
L. Sanchez-Cantu, H. N. Rode, T. J. Yun and N. V. Christou
Department of Surgery, McGill University, Montreal, Quebec, Canada.
Lethality and tumor necrosis factor production induced by different types
of lipopolysaccharide were studied in naive (non-primed) rats during the
late phase of endotoxin tolerance. The correlation with
antilipopolysaccharide antibodies was also analyzed. No correlation was
found between tumor necrosis factor levels and lipopolysaccharide-induced
mortality in naive animals. Low-toxicity lipopolysaccharide preparations
induced levels of tumor necrosis factor similar to those induced with more
toxic types of lipopolysaccharide. Late tolerance was associated with
progressively lower levels of lipopolysaccharide-induced tumor necrosis
factor and increasing titers of antilipopolysaccharide antibodies after
repeated injections of homologous lipopolysaccharide. During late
endotonxin tolerance, a direct correlation between the lipopolysaccharide
dose and peak tumor necrosis factor serum levels was found. We conclude
that since tumor necrosis factor serum levels do not correlate with
mortality, tumor necrosis factor alone cannot explain the lethal effect of
lipopolysaccharide.
