Abstract
Although initially described as an anti-tumor mediator, tumor necrosis factor-alpha (TNF) is generally considered as the master pro-inflammatory cytokine. It plays a crucial role in the pathogenesis of inflammatory diseases, such as rheumatoid arthritis (RA), inflammatory bowel disease, ankylosing spondylitis (AS), and psoriasis. Consequently, anti-TNF therapy has become mainstay treatment for autoimmune diseases. Historically, anti-inflammatory agents were developed before the identification of TNF. Salicylates, the active components of Willow spp., were identified in the mid-19th century for the alleviation of pain, fever, and inflammatory responses. Study of this naturally occurring compound led to the discovery of aspirin, which was followed by the development of non-steroidal anti-inflammatory drugs (NSAIDs) due to the chemical advances in the 19th–20th centuries. Initially, the most of NSAIDs were organic acid, but the non-acidic compounds were also identified as NSAIDs. Although effective in the treatment of inflammatory diseases, NSAIDs have some undesirable and adverse effect, such as ulcers, kidney injury, and bleeding in the gastrointestinal tract. In the past two decades, anti-TNF biologics were developed. Drugs belong to this class include soluble TNF receptor 2 fusion protein and anti-TNF antibodies. The introduction of anti-TNF therapeutics has revolutionized the management of autoimmune diseases, such as RA, psoriatic arthritis (PsA), plaque psoriasis (PP), AS, CD and ulcerative colitis (UC). Nevertheless, up to 40% of patients have no response to anti-TNF treatment. Furthermore, this treatment is associated with some adverse effects such as increased risk of infection, and even triggered the de novo development of autoimmune diseases. Such harmful effect of anti-TNF treatment is likely caused by the global inhibition of TNF biological functions. Therefore, specific inhibition of TNF receptor (TNFR1 or TNFR2) may represent a safer and more effective treatment, as proposed by some recent studies. In this review article, the historical development of anti-inflammatory drugs after World War II as briefly described above will be reviewed and analyzed. The future trend in the development of novel TNF receptor-targeting therapeutics will be discussed in the context of latest progress in the research of TNF biology.
Highlights
Autoimmune inflammatory diseases affect approximately 7.6– 9.4% of the world population, especially among the young and middle-aged women (Cooper et al, 2009; Bragazzi et al, 2016)
Non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids are effective in the alleviation of pain and inhibition of inflammation, while disease-modifying antirheumatic drugs (DMARDs) have the capacity of reducing tissue and organ damage caused by inflammatory responses (Tabas and Glass, 2013)
Traditional Non-selective NSAIDs Based on the chemical structure, the traditional non-selective NSAIDs can be classified into different sub-types (Antman et al, 2007): (1) salicylic acid derivatives: acetylsalicylic acid, diflunisal and sulfasalazine; (2) para-aminophenol derivatives: acetaminophen; (3) fenamates: mefenamic acid, meclofenamate, flufenamic acid; (4) propionic acid derivatives: ibuprofen, naproxen, fenoprofen, ketoprofen, flurbiprofen, oxaprozin; and (5) enolic acid derivatives: piroxicam, tenoxicam
Summary
Autoimmune inflammatory diseases affect approximately 7.6– 9.4% of the world population, especially among the young and middle-aged women (Cooper et al, 2009; Bragazzi et al, 2016). Non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, disease-modifying antirheumatic drugs (DMARDs) are traditionally used in the treatment of autoimmune inflammatory diseases. NSAIDs and glucocorticoids are effective in the alleviation of pain and inhibition of inflammation, while DMARDs have the capacity of reducing tissue and organ damage caused by inflammatory responses (Tabas and Glass, 2013). Treatment for RA and other autoimmune diseases has been revolutionized with the discovery that TNF is critically important in the development of the diseases (Monaco et al, 2015). Anti-TNF biologics (such as infliximab, adalimumab, etanercept, golimumab, and certolizumab pepol) have markedly improved the outcome of the management of autoimmune inflammatory diseases (Meier et al, 2013). Recent studies indicate that targeting of one of TNF receptors may represent a more effective and safer treatment for autoimmune disorders. The history of development of anti-inflammatory drugs, from small molecules to anti-TNF antibodies, will be discussed
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