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Tnf inhibitor

The meaning of «tnf inhibitor»

A TNF inhibitor is a pharmaceutical drug that suppresses the physiologic response to tumor necrosis factor (TNF), which is part of the inflammatory response. TNF is involved in autoimmune and immune-mediated disorders such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriasis, hidradenitis suppurativa and refractory asthma, so TNF inhibitors may be used in their treatment. The important side effects of TNF inhibitors include lymphomas, infections (especially reactivation of latent tuberculosis), congestive heart failure, demyelinating disease, a lupus-like syndrome, induction of auto-antibodies, injection site reactions, and systemic side effects.[1]

The global market for TNF inhibitors in 2008 was $13.5 billion[2] and $22 billion in 2009.[3]

Inhibition of TNF effects can be achieved with a monoclonal antibody such as infliximab[4] (Remicade), adalimumab (Humira), certolizumab pegol (Cimzia), and golimumab (Simponi), or with a circulating receptor fusion protein such as etanercept (Enbrel).

Thalidomide (Immunoprin) and its derivatives lenalidomide (Revlimid) and pomalidomide (Pomalyst, Imnovid) are also active against TNF.

While most clinically useful TNF inhibitors are monoclonal antibodies, some are simple molecules such as xanthine derivatives[5] (e.g. pentoxifylline)[6] and bupropion.[7] Bupropion is the active ingredient in the smoking cessation aid Zyban and the antidepressants Wellbutrin and Aplenzin.

Several 5-HT2A agonist hallucinogens including (R)-DOI, TCB-2, LSD and LA-SS-Az have unexpectedly also been found to act as potent inhibitors of TNF, with DOI being the most active, showing TNF inhibition in the picomolar range, an order of magnitude more potent than its action as a hallucinogen.[8][9][10]

The role of TNF as a key player in the development of rheumatoid arthritis was originally demonstrated by Kollias and colleagues in proof of principle studies in transgenic animal models.[11][12]

TNF levels have been shown to be raised in both the synovial fluid and synovium of patients with rheumatoid arthritis. This leads to local inflammation through the signalling of synovial cells to produce metalloproteinases and collagenase.[13]

Clinical application of anti-TNF drugs in rheumatoid arthritis was demonstrated by Marc Feldmann and Ravinder N. Maini, who won the 2003 Lasker Award for their work.[14] Anti-TNF compounds help eliminate abnormal B cell activity.[15][16]

Therapy which combines certain anti-TNF agents such as etanercept with DMARDs such as methotrexate has been shown to be more effective at restoring quality of life to sufferers of rheumatoid arthritis than using either drug alone.[13]

Clinical trials regarding the effectiveness of these drugs on hidradenitis suppurativa are ongoing.[17]

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