Relationship of Tumour Necrosis Factor and Endotoxin to Macrophage Cytotoxicity, Haemorrhagic Necrosis and Lethal Shock

  1. Gregory Bock Organizer and
  2. Joan Marsh
  1. Jay L. Rothstein and
  2. Hans Schreiber

Published Online: 28 SEP 2007

DOI: 10.1002/9780470513521.ch9

Ciba Foundation Symposium 131 - Tumour Necrosis Factor and Related Cytotoxins

Ciba Foundation Symposium 131 - Tumour Necrosis Factor and Related Cytotoxins

How to Cite

Rothstein, J. L. and Schreiber, H. (2007) Relationship of Tumour Necrosis Factor and Endotoxin to Macrophage Cytotoxicity, Haemorrhagic Necrosis and Lethal Shock, in Ciba Foundation Symposium 131 - Tumour Necrosis Factor and Related Cytotoxins (eds G. Bock and J. Marsh), John Wiley & Sons, Ltd., Chichester, UK. doi: 10.1002/9780470513521.ch9

Author Information

  1. Department of Pathology, University of Chicago, La Rabida Children's Hospital & Research Center, East 65th Street at Lake Michigan, Chicago, Illinois 60649, USA

Publication History

  1. Published Online: 28 SEP 2007

ISBN Information

Print ISBN: 9780471910978

Online ISBN: 9780470513521

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Keywords:

  • tumour necrosis factor;
  • endotoxin;
  • macrophage cytotoxicity;
  • haemorrhagic necrosis;
  • lethal shock

Summary

In this communication we discuss preliminary evidence suggesting a very strong synergism between tumour necrosis factor (TNF) and lipopolysaccharide (LPS) or between TNF and other bacteria in causing haemorrhagic necrosis and lethal shock. We found that TNF by itself does not cause haemorrhagic necrosis when injected into normal skin. TNF also had a rather low systemic toxicity when injected into disease-free, germfree-derived, defined-flora animals. On the other hand the addition of small amounts of LPS markedly raised the lethality of intravenous TNF treatments, and LPS injected into normal skin ‘prepared’ the site of injection for subsequent induction of haemorrhagic necrosis by locally injected TNF. Similar synergism was observed between TNF and mycoplasma. We suggest that the synergism between TNF and bacterial endotoxin (or other bacteria or bacterial products) may be part of an important defence mechanism against infections which is independent of specific immunity mediated by B and T cells. This synergism may be useful in increasing the therapeutic effects of TNF on tumours if the development of systemic toxicity in this treatment can be prevented.