Tumour necrosis factor a TNF

In other cases, the widespread application of a biopharmaceutical may be hindered by the occurrence of relatively toxic side effects (as is the case with tumour necrosis factor a (TNF-a, Chapter 9). Finally, some biomolecules have been discovered and purified because of a characteristic biological activity that, subsequently, was found not to be the molecule s primary biological activity. TNF-a again serves as an example. It was first noted because of its cytotoxic effects on some cancer cell types in vitro. Subsequently, trials assessing its therapeutic application in cancer proved disappointing due not only to its toxic side effects, but also to its moderate, at best, cytotoxic effect on many cancer cell types in vivo. TNF s major biological activity in vivo is now known to be as a regulator of the inflammatory response. 

The term cytokine was first introduced in the mid-1970s. It was applied to polypeptide growth factors controlling the differentiation and regulation of cells of the immune system. The interferons (IFNs) and interleukins (ILs) represented the major polypeptide families classified as cytokines at that time. Additional classification terms were also introduced, including lymphokines [cytokines such as interleukin-2 (IL-2) and interferon-y (IFN-y), produced by lymphocytes] and monokines [cytokines such as tumour necrosis factor-a (TNF-a) produced by monocytes]. However, classification on the basis of producing cell types also proved inappropriate, as most cytokines are produced by a range of cell types, e.g. both lymphocytes and monocytes produce IFN-a. 

THY-R, thyroid hormone receptor TIMP, tissue inhibitor of metalloprotease TK, tyrosine kinase TLC, thin layer chromatography TLRs, Toll-like receptors TMAOX, trimethylamine oxidase TMY tobacco mosaic virus TNF, tumour necrosis factor TNF-a, tumour necrosis factor-a TNF-a-RTK, tumour necrosis factor-a receptor tyrosine kinase TOPI, DNA topoisomerase I TOPII, DNA topoisomerase II t-PA, tissue plasminogen activator TPA, 12-Tetradecanoylphorbol 13-acetate... 

Armstrong L, Jordan N, Millar A. Interleukin 10 (IL-10) regulation of tumour necrosis factor a (TNF-a) from human alveolar macrophages and peripheral blood monocytes. Thorax 1996 51 143-9. 

Cytokines are chemicals released by damaged cells and cells involved in inflammation and repair. Drugs have been developed against two of them, tumour necrosis factor a (TNF-a) and interleukin 1 (IL-1). These two cytokines are released from macrophages and together they are key players in the inflammatory response. Levels of both are raised in rheumatoid arthritis and other autoimmune diseases. 

The dream of Stewart Adams, to find not only a palliative treatment but also a cure for rheumatoid diseases, did unfortunately not come true. [180] Pro-inflammatory cytokines like interleukin-1 and -6, or the tumour-necrosis factor-a (TNF-a) play key roles in diseases of the rheumatoid spectrum, and impact a multitude of signalling cascades within the immune system. Accumulating insight into the pathophysiology, biochemistry, cellular and molecular biology of these illnesses has clearly improved the opportunities for their treatment at the... 

Tumour necrosis factor-a (TNF-a) transiently increased intracellular superoxide and other reactive oxygen species production in human fibroblasts (Meier et al. 1989) and human oral carcinoma SCC-25 cells (Liu et al. 2000). 

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