Brouckaert P G, Everaerdt B, Libert C, Takahashi N, Fiers W
Laboratory of Molecular Biology, State University, Gent, Belgium.
Agents Actions. 1989 Jan;26(1-2):196-8. doi: 10.1007/BF02126607.
We compared the effects of human rTNF and murine rTNF in murine models of toxicity, esp. the induction of endotoxic shock. As was the case for the antitumour activity, we found a marked difference in activity between these two TNFs. Only murine rTNF was able to cause lethality, while human rTNF needed the synergistic action of sensitizing agents to become lethal. Further experiments, such as the study of IL-6 induction by TNF in mice, allowed us to distinguish two types of TNF effects: those that can equally well be exerted by human rTNF and by murine rTNF (type I effects) and those that can only be exerted by murine rTNF (type II effects). Both types of effects, the "toxic" (a type I effect) and the sensitizing (a type II effect) are needed to produce a lethal outcome. Other cytokines such as IL-1 and IFN-gamma, however, can also exert such a sensitizing effect and consequently lead to a fatal outcome when co-administered with human rTNF.
我们比较了人重组肿瘤坏死因子（rTNF）和鼠重组肿瘤坏死因子在鼠毒性模型中的作用，尤其是对内毒素休克的诱导作用。与抗肿瘤活性的情况一样，我们发现这两种肿瘤坏死因子在活性上存在显著差异。只有鼠重组肿瘤坏死因子能够导致致死性，而人重组肿瘤坏死因子需要致敏剂的协同作用才会变得具有致死性。进一步的实验，如研究肿瘤坏死因子在小鼠中诱导白细胞介素-6（IL-6）的情况，使我们能够区分两种类型的肿瘤坏死因子效应：人重组肿瘤坏死因子和鼠重组肿瘤坏死因子均可同等发挥的效应（I型效应）以及只能由鼠重组肿瘤坏死因子发挥的效应（II型效应）。产生致死性结果需要“毒性”（一种I型效应）和致敏（一种II型效应）这两种类型的效应。然而，其他细胞因子如白细胞介素-1和干扰素-γ，在与人重组肿瘤坏死因子共同给药时也可发挥这种致敏作用，从而导致致命结果。
