The biology of TNF blockade.
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.
Suryaprasad
Arun G
AG
Division of Gastroenterology, Department of Internal Medicine, University of California School of Medicine, Davis, CA 95616, USA.
Prindiville
T
T
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics; D003424:Crohn Disease / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D053473:Nod2 Signaling Adaptor Protein; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D014409:Tumor Necrosis Factor-alpha