TNF-alpha

Tumour necrosis factor is a polypeptide cytokine implicated in septic shock. It is produced primarily by mononuclear phagocytes. The stimulus for production includes immune complexes, bacteria and bacterial products including lipopolysaccharide endotoxin.

The effects of TNF are diverse:

• tumoricidal:
  • increased activation of phospholipases
  • free radical production
  • endonuclease nuclear DNA damage
• endothelium:
  • increased surface adhesion molecules
  • increased production of platelet activating factor, IL-1 and prostaglandins
  • pro-coagulant effect
• fibroblasts:
  • increased proliferation
  • increased protease, collagen and collagenase production
• monocyte, LAK, NK, neutrophil, B- and T-lymphocyte activation
• systemically:
  • pyrexia
  • increased acute phase proteins
  • decreased appetite
  • increased sleep
  • disordered metabolite handling: negative nitrogen balance, increased glucose release, wasting; hence the alternative term for TNF - cachectin

TNF has been used experimentally against human tumours with poor results due to the frequency of systemic side effects.