Tumor Necrosis Factor (TNF) related Diseases and Therapy

Tumor necrosis factors secreted by hematopoietic or non-hematopoietic cells are involved with inflammation and immunity as one kind of cytokines, as well as cell death and proliferation, differentiation, migration, phagocytosis, and survival.

However, aberrant TNF proteins can lead to a variety of disease states, including cancer, diabetes, atherosclerosis, and autoimmune disorders such as inflammatory bowel disease (IBD) and rheumatoid arthritis (RA). Furthermore, the connection between bacterial infection and autoimmune disorders resulting from TNF misregulation is reported. Although the pathogenic cause of most chronic inflammatory diseases is unknown, the classic inflammatory responses promoted by TNF are thought to account for them.

Since 1998, anti-TNF therapy has been used successfully for the treatment of inflammatory disease such as RA and IBD. The use of infliximab or adalimumab (two anti-TNF antibodies) and soluble TNF receptor fusion proteins fuel a major part of the global market as TNF inhibitors. Certolizumab pegol and golimumab are also used to treat crohn’s disease and RA later. However, the inhibition of TNF will lead an increased risk for bacterial infections. So people try to selectively inhibit TNF secreted from specific cell types. The strategy is to primary inhibit the pathogenic TNF but sparing essential TNF in the host defence.


Related literatures

1. Parameswaran N, Patial S. Tumor necrosis factor-α signaling in macrophages[J]. Critical Reviews™ in Eukaryotic Gene expression, 2010, 20(2).

2. den Broeder A, van de Putte L, Rau R, et al. A single dose, placebo controlled study of the fully human anti-tumor necrosis factor-alpha antibody adalimumab (D2E7) in patients with rheumatoid arthritis[J]. The Journal of rheumatology, 2002, 29(11): 2288-2298.

TNF receptors-CD molecules