TNF Blockade: An Inflammatory Issue

  • B. B. Aggarwal
  • S. Shishodia
  • Y. Takada
  • D. Jackson-Bernitsas
  • K. S. Ahn
  • G. Sethi
  • H. Ichikawa
Part of the Ernst Schering Research Foundation Workshop book series (SCHERING FOUND, volume 56)


Tumor necrosis factor (TNF), initially discovered as a result of its antitumor activity, has now been shown to mediate tumor initiation, promotion, and metastasis. In addition, dysregulation of TNF has been implicated in a wide variety of inflammatory diseases including rheumatoid arthritis, Crohn’s disease, multiple sclerosis, psoriasis, scleroderma, atopic dermatitis, systemic lupus erythematosus, type II diabetes, atherosclerosis, myocardial infarction, osteoporosis, and autoimmune deficiency disease. TNF, however, is a critical component of effective immune surveillance and is required for proper proliferation and function of NK cells, T cells, B cells, macrophages, and dendritic cells. TNF activity can be blocked, either by using antibodies (Remicade and Humira) or soluble TNF receptor (Enbrel), for the symptoms of arthritis and Crohn’s disease to be alleviated, but at the same time, such treatment increases the risk of infections, certain type of cancers, and cardiotoxicity. Thus blockers of TNF that are safe and yet efficacious are urgently needed. Some evidence suggests that while the transmembrane form of TNF has beneficial effects, soluble TNF mediates toxicity. In most cells, TNF mediates its effects through activation of caspases, NF- k B, AP-1, c-jun N-terminal kinase, p38 MAPK, and p44/p42 MAPK. Agents that can differentially regulate TNF expression or TNF signaling can be pharmacologically safe and effective therapeutics. Our laboratory has identified numerous such agents from natural sources. These are discussed further in detail.


Tumor Necrosis Factor Receptor Ursolic Acid Standardize Incidence Ratio Betulinic Acid Tumor Necrosis Factor Production 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2005

Authors and Affiliations

  • B. B. Aggarwal
    • 1
  • S. Shishodia
    • 2
  • Y. Takada
    • 2
  • D. Jackson-Bernitsas
    • 1
  • K. S. Ahn
    • 1
  • G. Sethi
    • 2
  • H. Ichikawa
    • 1
  1. 1.Cytokine Research Laboratory, Department of Experimental TherapeuticsUniversity of Texas, M.D. Anderson Cancer HospitalHosutonUSA
  2. 2.Cytokine Research Laboratory, Department of Experimental TherapeuticsThe University of Texas, M.D. Anderson Cancer CenterHoustonUSA

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