TNF inhibitor

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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]

Contents

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

Examples

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

Thalidomide and its derivatives lenalidomide and pomalidomide 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]

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]

Medical uses

Rheumatoid arthritis

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]

Skin disease

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

The National Institute of Clinical Excellence (NICE) has issued guidelines for the treatment of severe psoriasis using the anti-TNF drugs etanercept and adalimumab as well as the anti-IL12/23 biological treatment ustekinumab. In cases where more conventional systemic treatments such as psoralen combined with ultraviolet A treatment (PUVA), methotrexate, and ciclosporin have failed or can not be tolerated, these newer biological agents may be prescribed. Infliximab may be used to treat severe plaque psoriasis if aforementioned treatments fail or can not be tolerated. [18]

Gastrointestinal disease

In 2010 The National Institute of Clinical Excellence (NICE) in the UK issued guidelines for the treatment of severe Crohn's Disease with infliximab and adalimumab. [19]

Cancer

Anti-TNF therapy has shown only modest effects in cancer therapy. Treatment of renal cell carcinoma with infliximab resulted in prolonged disease stabilization in certain patients. Etanercept was tested for treating patients with breast cancer and ovarian cancer showing prolonged disease stabilization in certain patients via downregulation of IL-6 and CCL2. On the other hand, adding infliximab or etanercept to gemcitabine for treating patients with advanced pancreatic cancer was not associated with differences in efficacy when compared with placebo. [20]

Side effects

Cancer

The U.S. Food and Drug Administration continues to receive reports of a rare cancer of white blood cells (known as hepatosplenic T-cell lymphoma or HSTCL), primarily in adolescents and young adults being treated for Crohn's disease and ulcerative colitis with TNF blockers, as well as with azathioprine, and/or mercaptopurine. [21]

Opportunistic infections

TNF inhibitors put patients at increased risk of certain opportunistic infections. The FDA has warned about the risk of infection from two bacterial pathogens, Legionella and Listeria . People taking TNF blockers are at increased risk for developing serious infections that may lead to hospitalization or death due to certain bacterial, mycobacterial, fungal, viral, and parasitic opportunistic pathogens. [22]

Tuberculosis

In patients with latent Mycobacterium tuberculosis infection, active tuberculosis (TB) may develop soon after the initiation of treatment with infliximab. [23] Before prescribing a TNF inhibitor, physicians should screen patients for latent tuberculosis. The anti-TNF monoclonal antibody biologics infliximab, golimumab, certolizumab and adalimumab, and the fusion protein etanercept, which are all currently approved by the FDA for human use, have warnings which state that patients should be evaluated for latent TB infection, and if it is detected, preventive treatment should be initiated prior to starting therapy with these medications.

Fungal infections

The FDA issued a warning on September 4, 2008, that patients on TNF inhibitors are at increased risk of opportunistic fungal infections such as pulmonary and disseminated histoplasmosis, coccidioidomycosis, and blastomycosis. They encourage clinicians to consider empiric antifungal therapy in certain circumstances to all patients at risk until the pathogen is identified. [24] A recent review showed that anti-TNFα agents associate with increased infection risks for both endemic and opportunistic invasive fungal infections, particularly when given late in the overall course of treatment of the underlying disease, and in young patients receiving concomitant cytotoxic or augmented immunosuppressive therapy. [25]

Multiple sclerosis and demyelinating disorders

In 1999 a randomized control trial was conducted testing a TNF-alpha inhibitor prototype, Lenercept, for the treatment of multiple sclerosis (MS). However, the patients in the study who received the drug had significantly more exacerbations and earlier exacerbations of their disease than those who did not. [26] [27]

Case reports have also come out suggesting the possibility that anti-TNF-alpha agents not only may worsen, but may cause new-onset Multiple Sclerosis or other demyelinating disorders in some patients. [27] A 2018 case report described an Italian man with plaque psoriasis who developed MS after starting entanercept. Their literature review at that time identified 34 other cases of demyelinating disease developing after the initiation of an anti-TNF drug. [28] Thus, anti-TNF-alpha drugs are contraindicated in patients with MS, and the American Academy of Dermatology recommends avoiding their use in those with a first degree relative with MS. [29] [27]

Several other monoclonal antibodies like adalimumab, [30] [31] pembrolizumab, [32] nivolumab, and infliximab [33] have been reported to trigger MS as an adverse event. [34] [27]

The risk of anti-TNF-associated demyelination is not associated with genetic variants of multiple sclerosis. In some studies, there were clinical differences to multiple sclerosis as 70% of the patients with anti-TNF-induced demyelination. The symptoms of demyelination do not resolve with corticosteroids, intravenous immunoglobulin or plasma exchange, and is not clear whether MS therapies are effective in anti-TNF-induced demyelination. [35]

Paradoxical psoriasis

Despite their good safety profile, one of the common adverse events and side effects associated with TNF-α inhibitors is the occurrence of paradoxical psoriasis. [36] [37] [38] Paradoxical psoriasis is defined as the development of psoriatic lesions or as an exacerbation of pre-existent psoriatic lesions, in patients with or without a prior history of psoriasis, while undergoing treatment with TNF-α inhibitors, such as infliximab, adalimumab, and etanercept for their underlying inflammatory disease. [36] [37] [38] The first case of paradoxical psoriasis induced by TNF-α inhibitors was reported in a patient suffering from inflammatory bowel disease. [36] [37] [38] Subsequently, an increasing number of cases were reported in IBD cohorts and in patients suffering from other chronic immune-mediated inflammatory diseases such as rheumatoid arthritis. [36] [37] [38] This increase was positively correlated with the increasing use of TNF-α inhibitors. [36] [37] [38] The rates of paradoxical psoriasis reported across observational studies range from 2% to 5%, with higher rates observed in female patients. [36] [37] [38] The time to onset from induction therapy to development of psoriatic lesions can range from anywhere from a few days to a few months. [36] [37] [38] The most common clinical presentations are pustular psoriasis, plaque psoriasis and guttate psoriasis, with nail and scalp involvement. [36] [37] [38] Moreover, some patients may experience more than one type of psoriatic lesion and/or have lesions across multiple locations. [36] [37] [38]

Anti-TNF agents in nature

TNF or its effects are inhibited by several natural compounds, including curcumin [39] [40] [41] [42] (a compound present in turmeric), and catechins (in green tea). Cannabidiol [43] and Echinacea purpurea also seem to have anti-inflammatory properties through inhibition of TNF-α production, although this effect may be mediated through cannabinoid CB1 or CB2 receptor-independent effects. [44]

5-HT2A receptor agonists have also been shown to have potent inhibitory effects on TNF-α, including psilocybin found in many species of mushrooms. [45] [46]

Thymoquinone, a compound found in the flower Nigella sativa , has been studied for possible TNF-α inhibition and related benefits for autoimmune disorder treatment. [47] [48] [49] [50]

Isomyosamine, an isomer of myosmine, known by the brand name MYMD-1®, is a synthetic alkaloid derived from tobacco plant with potential lifespan extending properties that markedly outperformed rapamycin in a mouse longevity study. [51] MyMD-1 targets the root causes of inflammation and regulates the immuno-metabolic system through the modulation of numerous pro-inflammatory cytokines, including TNF-α, IL-6 and IL17A. [52]

History

Early experiments associated TNF with the pathogenesis of bacterial sepsis. Thus, the first preclinical studies using polyclonal antibodies against TNF-alpha were performed in animal models of sepsis in 1985 and showed that anti-TNF antibodies protected mice from sepsis. [53] [54] However, subsequent clinical trials in patients with sepsis showed no significant benefit. It wasn't until 1991 that studies in a transgenic mouse model of overexpressed human TNF provided the pre-clinical rationale for a causal role of TNF in the development of polyarthritis and that anti-TNF treatments could be effective against human arthritides. [11] This was later confirmed in clinical trials [55] and led to the development of the first biological therapies for rheumatoid arthritis.

Related Research Articles

<span class="mw-page-title-main">Psoriasis</span> Skin disease

Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by patches of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small localized patches to complete body coverage. Injury to the skin can trigger psoriatic skin changes at that spot, which is known as the Koebner phenomenon.

Rheumatology is a branch of medicine devoted to the diagnosis and management of disorders whose common feature is inflammation in the bones, muscles, joints, and internal organs. Rheumatology covers more than 100 different complex diseases, collectively known as rheumatic diseases, which includes many forms of arthritis as well as lupus and Sjögren's syndrome. Doctors who have undergone formal training in rheumatology are called rheumatologists.

<span class="mw-page-title-main">Tumor necrosis factor</span> Protein

Tumor necrosis factor is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homologous TNF domain.

<span class="mw-page-title-main">Immunosuppressive drug</span> Drug that inhibits activity of immune system

Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent the activity of the immune system.

<span class="mw-page-title-main">Infliximab</span> Biopharmaceutical drug for autommune disorders

Infliximab, a chimeric monoclonal antibody, sold under the brand name Remicade among others, is a medication used to treat a number of autoimmune diseases. This includes Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, and Behçet's disease. It is given by slow injection into a vein, typically at six- to eight-week intervals.

<span class="mw-page-title-main">Ankylosing spondylitis</span> Type of arthritis of the spine

Ankylosing spondylitis (AS) is a type of arthritis characterized by long-term inflammation of the joints of the spine, typically where the spine joins the pelvis. With AS, eye and bowel problems, and back pain may occur. Joint mobility in the affected areas sometimes worsens over time. Ankylosing spondylitis is believed to involve a combination of genetic and environmental factors. More than 90% of people affected in the UK have a specific human leukocyte antigen known as the HLA-B27 antigen. The underlying mechanism is believed to be autoimmune or autoinflammatory. Diagnosis is based on symptoms with support from medical imaging and blood tests. AS is a type of seronegative spondyloarthropathy, meaning that tests show no presence of rheumatoid factor (RF) antibodies.

<span class="mw-page-title-main">Psoriatic arthritis</span> Long-term inflammatory arthritis

Psoriatic arthritis (PsA) is a long-term inflammatory arthritis that occurs in people affected by the autoimmune disease psoriasis. The classic feature of psoriatic arthritis is swelling of entire fingers and toes with a sausage-like appearance. This often happens in association with changes to the nails such as small depressions in the nail (pitting), thickening of the nails, and detachment of the nail from the nailbed. Skin changes consistent with psoriasis frequently occur before the onset of psoriatic arthritis but psoriatic arthritis can precede the rash in 15% of affected individuals. It is classified as a type of seronegative spondyloarthropathy.

Etanercept, sold under the brand name Enbrel among others, is a biologic medical product that is used to treat autoimmune diseases by interfering with tumor necrosis factor (TNF), a soluble inflammatory cytokine, by acting as a TNF inhibitor. It has US Food and Drug Administration (FDA) approval to treat rheumatoid arthritis, juvenile idiopathic arthritis and psoriatic arthritis, plaque psoriasis and ankylosing spondylitis. Tumor necrosis factor alpha (TNFα) is the "master regulator" of the inflammatory (immune) response in many organ systems. Autoimmune diseases are caused by an overactive immune response. Etanercept has the potential to treat these diseases by inhibiting TNF-alpha.

Adalimumab, sold under the brand name Humira and others, is a disease-modifying antirheumatic drug and monoclonal antibody used to treat rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, plaque psoriasis, hidradenitis suppurativa, and uveitis. It is administered by subcutaneous injection. It works by inactivating tumor necrosis factor-alpha (TNFα).

<span class="mw-page-title-main">Certolizumab pegol</span> Pharmaceutical drug

Certolizumab pegol, sold under the brand name Cimzia, is a biopharmaceutical medication for the treatment of Crohn's disease, rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. It is a fragment of a monoclonal antibody specific to tumor necrosis factor alpha (TNF-α) and is manufactured by UCB.

<span class="mw-page-title-main">Biological therapy for inflammatory bowel disease</span>

Biological therapy, the use of medications called biopharmaceuticals or biologics that are tailored to specifically target an immune or genetic mediator of disease, plays a major role in the treatment of inflammatory bowel disease. Even for diseases of unknown cause, molecules that are involved in the disease process have been identified, and can be targeted for biological therapy. Many of these molecules, which are mainly cytokines, are directly involved in the immune system. Biological therapy has found a niche in the management of cancer, autoimmune diseases, and diseases of unknown cause that result in symptoms due to immune related mechanisms.

<span class="mw-page-title-main">Jan Vilček</span> Slovak immunologist (born 1933)

Jan T. Vilček is a Slovak-American biomedical scientist, educator, inventor and philanthropist. He is a professor in the department of microbiology at the New York University School of Medicine, and chairman and CEO of The Vilcek Foundation. Vilček received his M.D. degree from Comenius University Medical School in Bratislava in 1957; and his Ph.D. in Virology from the Institute of Virology, Czechoslovak Academy of Sciences, Bratislava, in 1962.

Biological response modifiers (BRMs) are substances that modify immune responses. They can be endogenous or exogenous, and they can either enhance an immune response or suppress it. Some of these substances arouse the body's response to an infection, and others can keep the response from becoming excessive. Thus they serve as immunomodulators in immunotherapy, which can be helpful in treating cancer and in treating autoimmune diseases, such as some kinds of arthritis and dermatitis. Most BRMs are biopharmaceuticals (biologics), including monoclonal antibodies, interleukin 2, interferons, and various types of colony-stimulating factors. "Immunotherapy makes use of BRMs to enhance the activity of the immune system to increase the body's natural defense mechanisms against cancer", whereas BRMs for rheumatoid arthritis aim to reduce inflammation.

<span class="mw-page-title-main">Golimumab</span> Pharmaceutical drug

Golimumab, sold under the brand name Simponi, is a human monoclonal antibody which is used as an immunosuppressive medication. Golimumab targets tumor necrosis factor alpha (TNF-alpha), a pro-inflammatory molecule and hence is a TNF inhibitor. Profound reduction in C-reactive protein (CRP) levels, interleukin (IL)-6, intercellaular adhesion molecules (ICAM)-1, matrix metalloproteinase (MMP)-3, and vascular endothelial growth factor (VEGF) demonstrates golimumab as an effective modulator of inflammatory markers and bone metabolism. Golimumab is given via subcutaneous injection.

Sir Marc Feldmann,, is an Australian-educated British immunologist. He is a professor at the University of Oxford and a senior research fellow at Somerville College, Oxford.

Olokizumab (OKZ) sold under the name Artlegia, is an immunosuppressive drug, used for the treatment of rheumatoid arthritis and COVID‑19. It is a humanized monoclonal antibody against the interleukin-6 (IL-6). IL-6 is a cytokine that plays an important role in immune response and is implicated in the pathogenesis of many diseases. Olokizumab is the first IL-6 inhibitor approved for treatment of rheumatoid arthritis which directly blocks cytokine instead of its receptor. Olokizumab specifically binds to IL-6 at site 3, blocking IL-6's ability to form a hexameric complex. Olokizumab was developed by R-Pharm group, and was launched in 2020.

<span class="mw-page-title-main">Apremilast</span> Medication for psoriasis and psoriatic arthritis

Apremilast, sold under the brand name Otezla among others, is a medication for the treatment of certain types of psoriasis and psoriatic arthritis. The drug acts as a selective inhibitor of the enzyme phosphodiesterase 4 (PDE4) and inhibits spontaneous production of TNF-alpha from human rheumatoid synovial cells. It is taken by mouth.

<span class="mw-page-title-main">Upadacitinib</span> Chemical compound (medication)

Upadacitinib, sold under the brand name Rinvoq, is a medication used for the treatment of rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, ulcerative colitis, Crohn's disease, ankylosing spondylitis, and axial spondyloarthritis. Upadacitinib is a Janus kinase (JAK) inhibitor that works by blocking the action of enzymes called Janus kinases. These enzymes are involved in setting up processes that lead to inflammation, and blocking their effect brings inflammation in the joints under control.

Otilimab is a fully human antibody which has been developed by the biotechnology company MorphoSys. It can also be referred to as HuCAL antibody, HuCAL standing for Human Combinatorial Antibody Library and being a technology used to generate monoclonal antibodies. Otilimab is directed against the granulocyte-macrophage colony stimulating factor (GM-CSF), a monomeric glycoprotein functioning as a cytokine promoting both proliferation and activation of macrophages and neutrophils.

<span class="mw-page-title-main">Antiarthritics</span> Drug class

An antiarthritic is any drug used to relieve or prevent arthritic symptoms, such as joint pain or joint stiffness. Depending on the antiarthritic drug class, it is used for managing pain, reducing inflammation or acting as an immunosuppressant. These drugs are typically given orally, topically or through administration by injection. The choice of antiarthritic medication is often determined by the nature of arthritis, the severity of symptoms as well as other factors, such as the tolerability of side effects.

References

  1. ↑ Scheinfeld N (September 2004). "A comprehensive review and evaluation of the side effects of the tumor necrosis factor alpha blockers etanercept, infliximab and adalimumab". The Journal of Dermatological Treatment. 15 (5): 280–294. doi:10.1080/09546630410017275. PMID   15370396. S2CID   43332215.
  2. ↑ Pappas DA, Bathon JM, Hanicq D, Yasothan U, Kirkpatrick P (September 2009). "Golimumab". Nature Reviews. Drug Discovery. 8 (9): 695–696. doi:10.1038/nrd2982. PMID   19721444.
  3. ↑ "Top Ten/Twenty Best Selling Drugs 2009". Archived from the original on 2011-09-17. Retrieved 2011-09-08.
  4. ↑ Scallon B, Cai A, Solowski N, Rosenberg A, Song XY, Shealy D, Wagner C (May 2002). "Binding and functional comparisons of two types of tumor necrosis factor antagonists". The Journal of Pharmacology and Experimental Therapeutics. 301 (2): 418–426. doi:10.1124/jpet.301.2.418. PMID   11961039. S2CID   43021140.
  5. ↑ Essayan DM (November 2001). "Cyclic nucleotide phosphodiesterases". The Journal of Allergy and Clinical Immunology. 108 (5): 671–680. doi:10.1067/mai.2001.119555. PMID   11692087. S2CID   21528985.
  6. ↑ Marques LJ, Zheng L, Poulakis N, Guzman J, Costabel U (February 1999). "Pentoxifylline inhibits TNF-alpha production from human alveolar macrophages". American Journal of Respiratory and Critical Care Medicine. 159 (2): 508–511. doi:10.1164/ajrccm.159.2.9804085. PMID   9927365.
  7. ↑ Brustolim D, Ribeiro-dos-Santos R, Kast RE, Altschuler EL, Soares MB (June 2006). "A new chapter opens in anti-inflammatory treatments: the antidepressant bupropion lowers production of tumor necrosis factor-alpha and interferon-gamma in mice". International Immunopharmacology. 6 (6): 903–907. doi:10.1016/j.intimp.2005.12.007. PMID   16644475.
  8. ↑ Miller KJ, Gonzalez HA (December 1998). "Serotonin 5-HT2A receptor activation inhibits cytokine-stimulated inducible nitric oxide synthase in C6 glioma cells". Annals of the New York Academy of Sciences. 861 (1): 169–173. Bibcode:1998NYASA.861..169M. doi:10.1111/j.1749-6632.1998.tb10188.x. PMID   9928254. S2CID   23264746.
  9. ↑ Yu B, Becnel J, Zerfaoui M, Rohatgi R, Boulares AH, Nichols CD (November 2008). "Serotonin 5-hydroxytryptamine(2A) receptor activation suppresses tumor necrosis factor-alpha-induced inflammation with extraordinary potency". The Journal of Pharmacology and Experimental Therapeutics. 327 (2): 316–323. doi:10.1124/jpet.108.143461. PMID   18708586. S2CID   25374241.
  10. ↑ Pelletier M, Siegel RM (December 2009). "Wishing away inflammation? New links between serotonin and TNF signaling". Molecular Interventions. 9 (6): 299–301. doi:10.1124/mi.9.6.5. PMC   2861806 . PMID   20048135.
  11. 1 2 Keffer J, Probert L, Cazlaris H, Georgopoulos S, Kaslaris E, Kioussis D, Kollias G (December 1991). "Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis". The EMBO Journal. 10 (13): 4025–4031. doi:10.1002/j.1460-2075.1991.tb04978.x. PMC   453150 . PMID   1721867.
  12. ↑ Brenner D, Blaser H, Mak TW (June 2015). "Regulation of tumour necrosis factor signalling: live or let die". Nature Reviews. Immunology. 15 (6): 362–374. doi:10.1038/nri3834. PMID   26008591. S2CID   1550839.
  13. 1 2 Ma X, Xu S (March 2013). "TNF inhibitor therapy for rheumatoid arthritis". Biomedical Reports. 1 (2): 177–184. doi:10.3892/br.2012.42. PMC   3956207 . PMID   24648915.
  14. ↑ Feldmann M, Maini RN (October 2003). "Lasker Clinical Medical Research Award. TNF defined as a therapeutic target for rheumatoid arthritis and other autoimmune diseases". Nature Medicine. 9 (10): 1245–1250. doi:10.1038/nm939. PMID   14520364. S2CID   52860838.
  15. ↑ Anolik JH, Ravikumar R, Barnard J, Owen T, Almudevar A, Milner EC, et al. (January 2008). "Cutting edge: anti-tumor necrosis factor therapy in rheumatoid arthritis inhibits memory B lymphocytes via effects on lymphoid germinal centers and follicular dendritic cell networks". Journal of Immunology. 180 (2): 688–692. doi: 10.4049/jimmunol.180.2.688 . PMID   18178805. S2CID   45744340.
  16. ↑ "A new view of drugs used to treat rheumatoid arthritis from medicineworld.org". medicineworld.org. Retrieved 16 April 2018.
  17. ↑ Haslund P, Lee RA, Jemec GB (November 2009). "Treatment of hidradenitis suppurativa with tumour necrosis factor-alpha inhibitors". Acta Dermato-Venereologica. 89 (6): 595–600. doi: 10.2340/00015555-0747 . PMID   19997689.
  18. ↑ "Psoriasis Association". psoriasis-association.org.uk. Retrieved 16 April 2018.
  19. ↑ "Infliximab and adalimumab for the treatment of Crohn's disease | 1-guidance | Guidance and guidelines | NICE". www.nice.org.uk. 19 May 2010. Retrieved 2016-12-04.
  20. ↑ Korneev KV, Atretkhany KN, Drutskaya MS, Grivennikov SI, Kuprash DV, Nedospasov SA (January 2017). "TLR-signaling and proinflammatory cytokines as drivers of tumorigenesis". Cytokine. 89: 127–135. doi:10.1016/j.cyto.2016.01.021. PMID   26854213.
  21. ↑ "FDA Alert: Tumor Necrosis Factor (TNF) blockers, Azathioprine and/or Mercaptopurine: Update on Reports of Hepatosplenic T-Cell Lymphoma in Adolescents and Young Adults". drugs.com. Retrieved 16 April 2018.
  22. ↑ "FDA Alert: Tumor Necrosis Factor-alpha (TNFα) Blockers: Label Change - Boxed Warning Updated for Risk of Infection from Legionella and Listeria". drugs.com. Retrieved 16 April 2018.
  23. ↑ Keane J, Gershon S, Wise RP, Mirabile-Levens E, Kasznica J, Schwieterman WD, et al. (October 2001). "Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent". The New England Journal of Medicine. 345 (15): 1098–1104. doi: 10.1056/NEJMoa011110 . PMID   11596589.
  24. ↑ "FDA: Manufacturers of TNF-Blocker Drugs Must Highlight Risk of Fungal Infections" (Press release). U.S. Food and Drug Administration (FDA). September 4, 2008. Retrieved 2009-11-15.
  25. ↑ Tragiannidis A, Kyriakidis I, Zündorf I, Groll AH (April 2017). "Invasive fungal infections in pediatric patients treated with tumor necrosis alpha (TNF-α) inhibitors". Mycoses. 60 (4): 222–229. doi:10.1111/myc.12576. PMID   27766695. S2CID   23722641.
  26. ↑ "TNF neutralization in MS: results of a randomized, placebo-controlled multicenter study. The Lenercept Multiple Sclerosis Study Group and The University of British Columbia MS/MRI Analysis Group". Neurology. 53 (3): 457–465. August 1999. doi: 10.1212/WNL.53.3.457 . PMID   10449104. S2CID   26126291.
  27. 1 2 3 4 Kemanetzoglou E, Andreadou E (April 2017). "CNS Demyelination with TNF-α Blockers". Current Neurology and Neuroscience Reports. 17 (4): 36. doi:10.1007/s11910-017-0742-1. PMC   5364240 . PMID   28337644.
  28. ↑ Napolitano M, Balato N, Ayala F, Cirillo T, Balato A (August 2018). "Multiple sclerosis following anti-tumor necrosis factor-alpha therapy for psoriasis: first case in Italy?". Giornale Italiano di Dermatologia e Venereologia. 153 (4): 567–572. doi:10.23736/S0392-0488.17.04992-6. PMID   25692775.
  29. ↑ Mansouri B, Horner ME, Menter A (August 2015). "Tumor Necrosis Factor-α Inhibitor Use in Psoriasis Patients With a First-degree Relative With Multiple Sclerosis". Journal of Drugs in Dermatology. 14 (8): 876–878. PMID   26267733.
  30. ↑ Engel S, Luessi F, Mueller A, Schopf RE, Zipp F, Bittner S (2 January 2020). "PPMS onset upon adalimumab treatment extends the spectrum of anti-TNF-α therapy-associated demyelinating disorders". Therapeutic Advances in Neurological Disorders. 13: 1756286419895155. doi:10.1177/1756286419895155. PMC   6940603 . PMID   31921355.
  31. ↑ Alnasser Alsukhni R, Jriekh Z, Aboras Y (2016-10-20). "Adalimumab Induced or Provoked MS in Patient with Autoimmune Uveitis: A Case Report and Review of the Literature". Case Reports in Medicine. 2016: 1423131. doi: 10.1155/2016/1423131 . PMC   5093248 . PMID   27840642.
  32. ↑ Romeo MA, Garassino MC, Moiola L, Galli G, Comi G, Martinelli V, Filippi M (December 2019). "Multiple sclerosis associated with pembrolizumab in a patient with non-small cell lung cancer". Journal of Neurology. 266 (12): 3163–3166. doi:10.1007/s00415-019-09562-z. PMID   31586260. S2CID   203654410.
  33. ↑ Kalinowska-Lyszczarz A, Fereidan-Esfahani M, Guo Y, Lucchinetti CF, Tobin WO (August 2020). "Pathological findings in central nervous system demyelination associated with infliximab". Multiple Sclerosis. 26 (9): 1124–1129. doi:10.1177/1352458519894710. PMC   7297659 . PMID   31845616.
  34. ↑ Garcia CR, Jayswal R, Adams V, Anthony LB, Villano JL (October 2019). "Multiple sclerosis outcomes after cancer immunotherapy". Clinical & Translational Oncology. 21 (10): 1336–1342. doi:10.1007/s12094-019-02060-8. PMC   6702101 . PMID   30788836.
  35. ↑ Williams I, Uhlig HH (December 2020). "Demyelination After Anti-TNF Therapy: Who is at Risk?". Journal of Crohn's & Colitis. 14 (12): 1651–1652. doi: 10.1093/ecco-jcc/jjaa144 . PMID   33026456.
  36. 1 2 3 4 5 6 7 8 9 Bucalo, Agostino; Rega, Federica; Zangrilli, Arianna; Silvestri, Valentina; Valentini, Virginia; Scafetta, Giorgia; Marraffa, Federica; Grassi, Sara; Rogante, Elena; Piccolo, Arianna; Cucchiara, Salvatore; Viola, Franca; Bianchi, Luca; Ottini, Laura; Richetta, Antonio (January 2020). "Paradoxical Psoriasis Induced by Anti-TNFα Treatment: Evaluation of Disease-Specific Clinical and Genetic Markers". International Journal of Molecular Sciences. 21 (21): 7873. doi: 10.3390/ijms21217873 . ISSN   1422-0067. PMC   7660646 . PMID   33114187. Creative Commons by small.svg  This article incorporates textfrom this source, which is available under the CC BY 4.0 license.
  37. 1 2 3 4 5 6 7 8 9 Vasconcellos, Jaqueline Barbeito de; Pereira, Daniele do Nascimento; Vargas, Thiago Jeunon de Sousa; Levy, Roger Abramino; Pinheiro, Geraldo da Rocha Castelar; Cursi, Ígor Brum (September–October 2016). "Paradoxical psoriasis after the use of anti-TNF in a patient with rheumatoid arthritis". Anais Brasileiros de Dermatologia. 91 (5 suppl 1): 137–139. doi:10.1590/abd1806-4841.20164456. ISSN   0365-0596. PMC   5325021 . PMID   28300922.
  38. 1 2 3 4 5 6 7 8 9 Toussirot, Éric; Aubin, François (2016-07-01). "Paradoxical reactions under TNF-α blocking agents and other biological agents given for chronic immune-mediated diseases: an analytical and comprehensive overview". RMD Open. 2 (2): e000239. doi:10.1136/rmdopen-2015-000239. ISSN   2056-5933. PMC   4964220 . PMID   27493788.
  39. ↑ Siddiqui AM, Cui X, Wu R, Dong W, Zhou M, Hu M, et al. (July 2006). "The anti-inflammatory effect of curcumin in an experimental model of sepsis is mediated by up-regulation of peroxisome proliferator-activated receptor-gamma". Critical Care Medicine. 34 (7): 1874–1882. doi:10.1097/01.CCM.0000221921.71300.BF. PMID   16715036. S2CID   71135736.
  40. ↑ Okunieff P, Xu J, Hu D, Liu W, Zhang L, Morrow G, et al. (July 2006). "Curcumin protects against radiation-induced acute and chronic cutaneous toxicity in mice and decreases mRNA expression of inflammatory and fibrogenic cytokines". International Journal of Radiation Oncology, Biology, Physics. 65 (3): 890–898. doi:10.1016/j.ijrobp.2006.03.025. PMID   16751071.
  41. ↑ Gulcubuk A, Altunatmaz K, Sonmez K, Haktanir-Yatkin D, Uzun H, Gurel A, Aydin S (February 2006). "Effects of curcumin on tumour necrosis factor-alpha and interleukin-6 in the late phase of experimental acute pancreatitis". Journal of Veterinary Medicine. A, Physiology, Pathology, Clinical Medicine. 53 (1): 49–54. doi:10.1111/j.1439-0442.2006.00786.x. PMID   16411910.
  42. ↑ Lantz RC, Chen GJ, Solyom AM, Jolad SD, Timmermann BN (June 2005). "The effect of turmeric extracts on inflammatory mediator production". Phytomedicine. 12 (6–7): 445–452. doi:10.1016/j.phymed.2003.12.011. PMID   16008121.
  43. ↑ Mechoulam R, Peters M, Murillo-Rodriguez E, Hanus LO (August 2007). "Cannabidiol--recent advances". Chemistry & Biodiversity. 4 (8): 1678–1692. doi:10.1002/cbdv.200790147. PMID   17712814. S2CID   3689072.
  44. ↑ Raduner S, Majewska A, Chen JZ, Xie XQ, Hamon J, Faller B, et al. (May 2006). "Alkylamides from Echinacea are a new class of cannabinomimetics. Cannabinoid type 2 receptor-dependent and -independent immunomodulatory effects". The Journal of Biological Chemistry. 281 (20): 14192–14206. doi: 10.1074/jbc.M601074200 . PMID   16547349. S2CID   1570400.
  45. ↑ Nkadimeng SM, Steinmann CM, Eloff JN (2021). "Anti-Inflammatory Effects of Four Psilocybin-Containing Magic Mushroom Water Extracts in vitro on 15-Lipoxygenase Activity and on Lipopolysaccharide-Induced Cyclooxygenase-2 and Inflammatory Cytokines in Human U937 Macrophage Cells". Journal of Inflammation Research. 14: 3729–3738. doi: 10.2147/JIR.S317182 . PMC   8352634 . PMID   34385833.
  46. ↑ Nau F, Yu B, Martin D, Nichols CD (2013-10-02). "Serotonin 5-HT2A receptor activation blocks TNF-α mediated inflammation in vivo". PLOS ONE. 8 (10): e75426. Bibcode:2013PLoSO...875426N. doi: 10.1371/journal.pone.0075426 . PMC   3788795 . PMID   24098382.
  47. ↑ Umar S, Hedaya O, Singh AK, Ahmed S (September 2015). "Thymoquinone inhibits TNF-α-induced inflammation and cell adhesion in rheumatoid arthritis synovial fibroblasts by ASK1 regulation". Toxicology and Applied Pharmacology. 287 (3): 299–305. doi:10.1016/j.taap.2015.06.017. PMC   4549173 . PMID   26134265.
  48. ↑ Farkhondeh T, Samarghandian S, Shahri AM, Samini F (2018). "The Neuroprotective Effects of Thymoquinone: A Review". Dose-Response. 16 (2): 1559325818761455. doi:10.1177/1559325818761455. PMC   5898665 . PMID   29662431.
  49. ↑ Ali MY, Akter Z, Mei Z, Zheng M, Tania M, Khan MA (February 2021). "Thymoquinone in autoimmune diseases: Therapeutic potential and molecular mechanisms". Biomedicine & Pharmacotherapy. 134: 111157. doi: 10.1016/j.biopha.2020.111157 . PMID   33370631. S2CID   229714190.
  50. ↑ Malik S, Singh A, Negi P, Kapoor VK (November 2021). "Thymoquinone: A small molecule from nature with high therapeutic potential". Drug Discovery Today. 26 (11): 2716–2725. doi:10.1016/j.drudis.2021.07.013. PMID   34303824. S2CID   236431672.
  51. ↑ Sabini, E., O'Mahony, A., & Caturegli, P. (2022). MyMD-1 Improves Health Span and Prolongs Life Span in Old Mice: A Noninferiority Study to Rapamycin. The Journals of Gerontology: Series A. PMID   35914953 doi : 10.1093/gerona/glac142
  52. ↑ Di Dalmazi, G., Chalan, P., & Caturegli, P. (2019). MYMD-1, a novel immunometabolic regulator, ameliorates autoimmune thyroiditis via suppression of Th1 responses and TNF-α release. The Journal of Immunology, 202(5), 1350-1362. PMID   30674573 doi : 10.4049/jimmunol.1801238
  53. ↑ Vilcek J (July 2008). "First demonstration of the role of TNF in the pathogenesis of disease". Journal of Immunology. 181 (1): 5–6. doi: 10.4049/jimmunol.181.1.5 . PMID   18566362. S2CID   44529219.
  54. ↑ Beutler B, Milsark IW, Cerami AC (July 2008). "Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science, 1985, 229(4716):869-871. Classical article". Journal of Immunology. 181 (1): 7–9. doi:10.1126/science.3895437. PMID   18566363.
  55. ↑ Elliott MJ, Maini RN, Feldmann M, Kalden JR, Antoni C, Smolen JS, et al. (October 1994). "Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis". Lancet. 344 (8930): 1105–1110. doi:10.1016/S0140-6736(94)90628-9. PMID   7934491. S2CID   22776233.
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