USMLE

TNF-alpha

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Cytokines
  1. TNF-alpha
  2. IL-1
  3. IL-2
  4. IL-3
  5. IL-4
  6. IL-5
  7. IL-6
  8. IL-8
  9. IL-10
  10. IL-12
  11. TGF-beta
  12. IFN-alpha and IFN-beta
  13. IFN-gamma

Summary

Tumor necrosis factor-alpha (TNFα), also known as cachexin, or cachectin, is one of the chief cytokines involved in systemic inflammation and the acute phase reaction. As a cell signalling protein, it activates many other types of immune cells to potentiate inflammation. As a pyrogen, it works on hypothalamic nuclei to increase body temperature. TNF-alpha secreted by tumors is also implicated in paraneoplastic cachexia syndrome.

Key Points

  • Tumor Necrosis Factor-alpha (TNF-alpha)
    • Secreted by Macrophages
      • As well as mast cells, to a lesser degree
    • Actions
      • Induces fever
        • Signalling at hypothalamic nuclei increase body temperature
      • Promotes inflammation
        • Along with IL-1 and IL-6, TNF-alpha induces the systemic inflammatory response (SIRS) and sepsis, and causes hepatic release of acute-phase reactants (e.g. C-reactive protein and fibrinogen).
        • Activates endothelium to increase vascular leak and causes WBC recruitment
      • Implicated in paraneoplastic cachexia
        • TNF-alpha secreted by tumors
      • Target of many anti-inflammatory or anti-rheumatic drugs
        • Infliximab (chimeric monoclonal antibody)
        • Certolizumab (pegylated humanized antibody)
        • Etanercept (recombinant decoy receptor)