Comparative activity of human and murine tumor necrosis factor in toxicity and anti-infectious assays in mice

In comparative experiments, the lethal effect of rHuTNF or rMuTNF was evaluated in animals sensitized by adrenalectomy or galactosamine treatment. No clear-cut difference was observed in the effective dose irrespective of the origin of the TNF preparation in Swiss or in C3H/HeJ mice. The latter mouse substrain known to be a low responder to LPS was used in the assays to evaluate the influence of LPS contamination in TNF-induced responses. Like LPS, TNF was shown to induce abortion in pregnant mice, and the mortality rate of foetuses was almost the same in animals challenged with either rHuTNF or rMuTNF. No species preference was apparent in the protective effect of TNF against a bacterial challenge. In adult mice subsequently infected with Klebsiella pneumoniae or Listeria monocytogenes, the survival rate was comparable in groups treated with both TNF preparations. In contrast, in young mice rHuTNF and rMuTNF were ineffective against Listeria and poorly active against Klebsiella organisms, whereas a significant effect was obtained with crude mouse serum containing TNF.