Abstract
Tumor-bearing animals are known to have increased susceptibility to toxic effects of lipopolysaccharide (LPS). However mechanisms of this phenomenon are so far not clear. We studied the effects of substances from the serum of tumor-bearing mice on the sensitivity of intact animals to the acute lethal effects of LPS and muramyl dipeptide (MDP) combination. We found that i.v. administration of serum fractions of tumor-bearers with mol. weight 10-30, 100-300 and > 300 kDa results in increased lethality and 1000-fold increased production of tumor necrosis factor (TNF) after administration of LPS and MDP combination. It has been proved that adherent splenocytes in the presence of LPS and MDP are responsible for the enhanced production of TNF by mice presensitized with serum from tumor bearers. At the same time the ability for production of TNF by non-adherent splenocytes and peritoneal cells was not changed. We have demonstrated that substances present in the serum of tumor-bearers used for sensitising of intact animals, not only stimulates enhanced production of TNF by definite cells of the recipients, but increases the sensitivity of the recipients to the toxic effects of recombinant human TNF-alpha.
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