Tumor necrosis factor treatment

Plant D, Bowes J, Potter C, Hyrich KL, Morgan AW, Wilson AG et al (2011) Genome-wide association study of genetic predictors of anti-tumor necrosis factor treatment efficacy in rheumatoid arthritis identifies associations with polymorphisms at seven loci. Arthritis Rheum 63 645-653... 

Cytokines, eg, interferons, interleukins, tumor necrosis factor (TNF), and certain growth factors, could have antitumor activity directiy, or may modulate cellular mechanisms of antitumor activity (2). Cytokines may be used to influence the proliferation and differentiation of T-ceUs, B-ceUs, macrophage—monocyte, myeloid, or other hematopoietic cells. Alternatively, the induction of interferon release may represent an important approach for synthetic—medicinal chemistry, to search for effective antiinflammatory and antifibrotic agents. Inducers of interferon release may also be useful for lepromatous leprosy and chronic granulomatous disease. The potential cytokine and cytokine-related therapeutic approaches to treatment of disease are summarized in Table 4. A combination of cytokines is a feasible modaUty for treatment of immunologically related diseases however, there are dangers inherent in such an approach, as shown by the induction of lethal disserninated intravascular coagulation in mice adrninistered TNF-a and IFN-y. 

Cytokines and biological response modifiers represent a broad class of therapeutic agents that modify the hosts response to cancer or cancer therapies. The enormous body information about their clinical uses and their side effects is beyond the scope of this essay that can only give illustrative examples. For an up-to-date information the reader can resort to reference [5]. As many as 33 different interleukins are known and the list continues to grow IL-2 used in the treatment of kidney cancer is one example. Interferon alpha is used for chronic myelogenous leukeia, hairy cell leukaemia and Kaposi s sarcoma. Interferons are also used in the treatment of chronic infections such as viral hepatitis. Tumor necrosis factor (alpha), G/GM/M-CSF, and several other cellular factors are used in treatment of various cancers. Many of these cytokines produce serious side effects that limit their use. 

Fig. 14 Effect of the molecular weight of tamarind seed xyloglucan depolymerized by ( ) 7-irradiation, ( ) ultrasonication, and ( ) endo-glucanase treatment on the production of various cytokines (Tumor necrosis factor a, TNE-a Interleukin 8, IL-8 Interleukin 10, IL-10 and Interleukin 12, IL-12) in HaCaT cells (Immortalized keratinocytes line) [301]...

Yamashita reported anti-inflammatory effect of astaxanthin when administered with aspirin. An oral preparation has been developed by Alejung and Wadstroem for the treatment of Helicobacter infections of the mammalian gastrointestinal tract. Strong evidence suggested that astaxanthin modulated the humoral and non-humoral immune systems. It enhanced the release of interleukin-1 and tumor necrosis factor-... 

Turner, P.F., Rockett, K.A., Ottesen, E.A., Francis, H., Awadzi, K. and Clark, I.A. (1994) Interleukin-6 and tumor necrosis factor in the pathogenesis of adverse reactions after treatment of lymphatic filariasis and onchocerciasis. Journal of Infectious Diseases 169, 1071-1075. 

Wolf, P. et al., Topical treatment with liposomes containing T4 endonuclease V protects human skin in vivo from ultraviolet-induced upregulation of interleukin-10 and tumor necrosis factor-alpha, J. Invest. Dermatol. 114, 149-156, 2000. 

As in any safety evaluation, the planned work should be related to the intended use and treatment of humans, for example one dose in a few gravely ill patients or multiple doses of the entire healthy community as prophylaxis against a trivial condition. Contrast, say, what might be appropriate for tumor necrosis factor, as in an experimental trial in a few sufferers from late-stage cancer, with the requirements... 

Examples of the early application of recombinant DNA technology in medicine are the development of recombinant human growth hormone human insulin human interferons, thought to have anticancer activity in addition to antiviral activity interleukins (regulatory proteins from lymphocytes that are believed to be important in the treatment of immunodeficiency diseases and cancer) tumor necrosis factor epidermal and bone marrow progenitor cell growth factors and the production of vaccines (Table 12.1). 

There is a great deal of evidence that AmB can exert a number of effects directly on cells of the immune system, and particularly on macrophages to increase nonspecific defense mechanisms against pathogens and cancer cells. These mechanisms include the production of nitric oxide (NO) (32) and tumor necrosis factor alpha (TNF-a) (33), which could contribute to the antifungal and antiparasitic activity of AmB. However, excess TNF-a production could also be responsible for some of the side effects associated with AmB treatment, such as fever and chills. 

Keystone, E. C., Kavanaugh, A. E., Sharp, J. T., et al. (2004) Radiographic, cUnical, and functional outcomes of treatment with adaUmumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy a randomized, placebo-controUed, 52-week trial. Arthritis and Rheumatism. 50, 1400-1411. 

Tumor necrosis factor-a (TNF-a) is a critical mediator of inflammation in autoimmune diseases like Crohn s disease and rheumatoid arthritis. Infliximab binds TNF-a and prevents its binding to the TNF receptor for treatment of these diseases. 

Etanercept is a recombinant human soluble tumor necrosis factor-alpha (TNFo ) receptor fusion protein that binds to TNFo and decreases its role in disorders involving excess inflammation. It is approved for subcutaneous use in the treatment of patients with moderate to severe active rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, ankylosing arthritis and plaque psoriasis. To the adverse reactions mentioned for infliximab, rare reports of congestive heart failure should be added. 

TNFr-II (Etanercept or Enbrel) Tumor necrosis factor (TNF) receptor II (p75) Binds to TNF and neutralizes its biologic activities IgGi Fc sequences Increases half-life of the final prodnct dne to Fc recognition seqnences Provides improved TNFr half-life (from 20 minntes to 73 hours) (data from BLA of Enbrel) Approved for treatment of rhenmatoid arthritis... 

Imiquimod (Aldara) is an immunomodulator approved for the treatment of external genital and perianal warts in adults, actinic keratoses on the face and scalp, and biopsy-proven primary basal cell carcinomas on the trunk, neck, and extremities. The mechanism of its action is thought to be related to imiquimod s ability to stimulate peripheral mononuclear cells to release interferon- and to stimulate macrophages to produce interleukins-1, -6, and -8, and tumor necrosis factor- (TNF-k). 

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