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)