Reactome | TNF-alpha inhibitors bind to soluble TNF trimer

TNF-alpha inhibitors bind to soluble TNF trimer

Stable Identifier

R-HSA-9714924

Type

Reaction [binding]

Species

Homo sapiens

Compartment

extracellular region

ReviewStatus

5/5

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TNF-alpha inhibitors bind to soluble TNF trimer

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Clinical evidence and experimental studies in rodents suggest that signaling by soluble TNF (as shown here) is associated with chronic and excessive inflammation in autoimmune diseases, whereas signaling by the membrane form plays an essential role in resolving inflammation and maintaining immunity toward pathogens, especially to Mycobacterium tuberculosis (Perrier et al, 2013). The available TNF-alpha inhibitors (aducanumab, infliximab, certolizumab, etanercept, golimumab) neutralize both the soluble and the membrane form, which explains the increased susceptibility to infections. They are approved for juvenile and adult rheumatic and psoriatic arthritis, Crohn's disease, ulcerative colitis, ankylosing spondylitis, and several other rare diseases. Main side effects can be infections, lymphoma, congestive heart failure, a lupuslike syndrome, induction of auto-antibodies and injection site reactions. The incidence of all these effects is very low, however (Scheinfeld, 2004).

Literature References

PubMed ID	Title	Journal	Year
21091114	Anti-TNF-α agents in the treatment of immune-mediated inflammatory diseases: mechanisms of action and pitfalls Silva, LC, Ortigosa, LC, Benard, G	Immunotherapy	2010
17636564	Mechanism of action of certolizumab pegol (CDP870): in vitro comparison with other anti-tumor necrosis factor alpha agents Nesbitt, A, Fossati, G, Bergin, M, Stephens, P, Stephens, S, Foulkes, R, Brown, D, Robinson, M, Bourne, T	Inflamm Bowel Dis	2007