The Biology of Cachectin/Tumor Necrosis Factor

  • K. J. Tracey
  • A. Cerami


The immune system produces cytokines and other humoral factors to protect the host when threatened by inflammatory agents, microbial invasion, or injury. In some cases this complex defense network successfully restores normal homeostasis, but at other times the overproduction of participating immunoregulatory mediators may be deleterious. Some examples of immune system-mediated injury have been extensively investigated including anaphylactic shock, autoimmune disease, and immune complex disorders. More recently it has become clear that the cytokine cachectin/tumor necrosis factor (TNF) occupies a key role in the pathological physiology associated with diverse inflammatory states and other serious illnesses including septic shock and cachexia. For example, when cachectin/TNF is produced by resident macrophages during early microbial infection it mediates an inflammatory response that may alienate and repel the attacking organisms. If the infection spreads, however, the subsequent release of large quantities of cachectin/TNF into the circulation is catastrophic and triggers a state of lethal shock. These toxic effects occur by direct effects on host cells and by interactions with a cascade of other endogenous mediators including interleukin-1 and interferon-γ. Here we briefly review the history and biology of cachectin/TNF, and discuss the potential for modulating the effects of this pluripotent molecule in a variety of pathologic states.


Tumor Necrosis Factor Septic Shock Human Tumor Necrosis Factor Endogenous Pyrogen Lethal Shock 
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© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • K. J. Tracey
  • A. Cerami

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