Targeting sTNF/TNFR1 Signaling as a New Therapeutic Strategy

Deregulation of the tumor necrosis factor (TNF) plays an important role in the initiation and perpetuation of chronic inflammation and has been implicated in the development of various autoimmune diseases. Accordingly, TNF-inhibitors are successfully used for the treatment of several diseases, such...

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Bibliographic Details
Published in:Antibodies 2015-03, Vol.4 (1), p.48-70
Main Authors: Fischer, Roman, Kontermann, Roland, Maier, Olaf
Format: Article
Language:English
Subjects:
antibodies
autoimmune diseases
Deregulation
inflammation
neurodegeneration
Psoriasis
Rheumatoid arthritis
Skin diseases
TNF
TNF receptors
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Summary:Deregulation of the tumor necrosis factor (TNF) plays an important role in the initiation and perpetuation of chronic inflammation and has been implicated in the development of various autoimmune diseases. Accordingly, TNF-inhibitors are successfully used for the treatment of several diseases, such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis. However, total inhibition of TNF can cause severe side effects such as an increased risk of inflammation and reactivation of tuberculosis. This is likely due to the different actions of the two TNF receptors. Whereas TNFR1 predominantly promotes inflammatory signaling pathways, TNFR2 mediates immune modulatory functions and promotes tissue homeostasis and regeneration. Therefore, the specific blockage of TNFR1 signaling, either by direct inhibition with TNFR1-selective antagonists or by targeting soluble TNF, which predominantly activates TNFR1, may prevent the detrimental effects associated with total TNF-inhibitors and constitute a next-generation approach to interfere with TNF.
ISSN:2073-4468
2073-4468
DOI:10.3390/antib4010048