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Protection against a lethal dose of endotoxin by an inhibitor of tumour necrosis factor processing.

Authors
  • Mohler, K M
  • Sleath, P R
  • Fitzner, J N
  • Cerretti, D P
  • Alderson, M
  • Kerwar, S S
  • Torrance, D S
  • Otten-Evans, C
  • Greenstreet, T
  • Weerawarna, K
Type
Published Article
Journal
Nature
Publication Date
Jul 21, 1994
Volume
370
Issue
6486
Pages
218–220
Identifiers
PMID: 8028669
Source
Medline
License
Unknown

Abstract

Tumour necrosis factor (tumour necrosis factor-alpha/cachectin) plays a critical role in certain physiological defensive responses but causes severe damage to the host organism when produced in excess. 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 cleavage. The two forms of tumour necrosis factor and lymphotoxin-alpha (tumour necrosis factor-beta/lymphotoxin), a related protein, have similar but apparently not identical biological activities. A therapeutic agent which inhibited the release of tumour necrosis factor, but did not reduce the cell-associated activity or the level of lymphotoxin-alpha, 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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