Abstract
TUMOUR necrosis factor (tumour necrosis factor-α/cachectin) plays a critical role in certain physiological defensive responses but causes severe damage to the host organism when produced in excess1. There are two forms of tumour necrosis factor, a type II membrane protein of relative molecular mass 26,000 (26K) and a soluble, 17K form generated from the cell-bound protein by proteolytic cleavage2,3. The two forms of tumour necrosis factor and lymphotoxin-α (tumour necrosis factor-β/lymphotoxin), a related protein, have similar but apparently not identical biological activities4–6. A therapeutic agent which inhibited the release of tumour necrosis factor, but did not reduce the cell-associated activity or the level of lymphotoxin-α, might preserve the benefits of these cytokines while preventing tumour necrosis factor-induced damage. Here we describe a potent inhibitor of tumour necrosis factor processing and report that it protects mice from a lethal dose of endotoxin.
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Mohler, K., Sleath, P., Fitzner, J. et al. Protection against a lethal dose of endotoxin by an inhibitor of tumour necrosis factor processing. Nature 370, 218–220 (1994). https://doi.org/10.1038/370218a0
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DOI: https://doi.org/10.1038/370218a0
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