The biology of TNF blockade

Autoimmun Rev. 2003 Oct;2(6):346-57. doi: 10.1016/s1568-9972(03)00048-x.


Rheumatoid arthritis and Crohn's disease are costly diseases that result in significant long-term patient disability. They are chronic inflammatory diseases that are associated with increased production of Tumor Necrosis Factor (TNF). Blockage of this cytokine with bio-engineered compounds has significantly changed therapy of these diseases and has ushered in the era of biological therapy. The pro-inflammatory role of TNF is mediated by its essential respiratory burst function that is effectively inhibited by anti-TNF therapy. Anti-TNF therapy is effective in approximately two-thirds of patients to whom it is administered, but the effect is temporary. Lack of response to anti-TNF therapy stems from interplay of host-factors including: host cytokine response, disease phenotype, and antibody response to the anti-TNF agents. NOD 2, a defect present in approximately 50% of Crohn's disease patients, bears no relationship to non-response. Additionally, TNF promoter gene polymorphisms and TNF receptor gene heterogeneity play a significant role in non-response and disease course/severity. Adverse effects of anti-TNF therapy include early and delayed hypersensitivity reactions, cell-mediated infections, lupus-like syndrome, demyelinating diseases, and exacerbation of CHF.

Publication types

  • Review

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / immunology
  • Carrier Proteins / genetics
  • Crohn Disease / drug therapy
  • Crohn Disease / immunology
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Nod2 Signaling Adaptor Protein
  • Polymorphism, Genetic
  • Promoter Regions, Genetic
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / genetics


  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein
  • Tumor Necrosis Factor-alpha