Cytokine tumour necrosis factor

An interesting additional point is that during trauma the cytokine, tumour necrosis factor, results in a decrease in lipase activity in adipose and other tissues, so that there is an increase in the level of VLDL and chylomicrons in the blood. The significance of this is unclear but it may be that pathogens in the blood are adsorbed onto the emulsion of VLDL or chylomicrons which reduces the risk of adsorption of the pathogen onto the surface of a cell, which is necessary for the pathogen to enter the ceU. This localisation also aids attack by antibodies (Chapter 17). 

Increased plasma concentrations of glucocorticoids and proinflammatory cytokines (tumour necrosis factor and some interleukins) produced by both tumour cells and macrophages within the tumour stimulate hpolysis and protein degradation. This is accompanied by low levels of insuhn which also encourage hpolysis and proteolysis. 

COSTA, J.J., MATOSSIAN, K RESNICK, M.B., BEIL, W.J., WANG, D.T., GORDON, J.R., DVORAK, A.M., WELLER, P.F. GALLI, S.J. (1993) Human eosinophils can express the cytokines tumour necrosis factor-a and macrophage inflammatory protein-la. Journal of Clinical Investigation, 91, 2673-2684. 

Then, in a publication in 2005, it was shown - by the use of specific drugs known to block the different receptors - that these effects were most likely the result of CRF acting specifically on the CRFR1 receptor and not on CRFR2.44 Most recently, it has been shown that this effect is dependent on the release of the cytokine tumour necrosis factor alpha (TNFa) following SEA administration. Normal mice injected with SEA were shown to have increased activity in relevant areas of the brain whereas mice unable to produce TNF (TNF / knockout mice) did not show this after challenge with SEA but still showed brain responses to other stressors. As might be expected ... 

Elderberry extracts have been tested for immunomodulatory activity on monocytes from healthy individuals [44]. An increase in their cytokine production was observed in vitro following stimulation. The production of inflammatory cytokines was tested using blood derived monocytes from 12 healthy human donors in vitro. Elderberry extracts and lipopolysaccharid (as a positive control for monocyte activation) were added to the monocytes and incubated. The results show an increase in secretion of proinflammatory cytokines (tumour necrosis factor-alpha and interleukins IL-ip, IL6, and IL-8), and the stimulatory activity was dose dependent. Standardized elderberry extract showed the highest cytokine stimulation. 

During ischaemia, NOS is activated by calcium influx or by cytokines like tumour necrosis factor (TNF) or by lipopolysaccharide (LPS) and NO is produced in excess. It has been proposed that the excitotoxic effect of glutamate, which contributes to ischaemia-induced neuronal damage, is mediated by increased production of NO via a chain of events that includes increases in intracellular calcium (via glutamate activation of NMDA receptors), calcium activation of NOS, production of NO and peroxynitrite, and induction of lipid peroxidation. In fact, N-nitro-L-atginine, a selective inhibitor of NOS, has been shown to prevent glutamate-induced neurotoxicity in cortical cell cultures (Dawson rf /., 1991). 

Garside, P., Bunce, C., Tomlinson, R.C., Nichols, B.L. and Mowat, A.M. (1993) Analysis of enteropathy induced by tumour necrosis factor alpha. Cytokine 5, 24-30. 

In addition to directly eliciting cell chemotaxis and free-radical production, PAF can also induce the release of various inflammatory cytokines, amongst which tumour necrosis factor (TNF) is of particular importance [ 312 ]. We have recently shown that PAF stimulates TNF production from peripheral blood derived monocytes and at picomolar concentrations amplifies lipopoly-saccharide (LPS)-induced TNF production, effects inhibited by various PAF antagonists [313]. PAF also acts synergistically with interferon-y (IFN-y) to increase the monocyte cytotoxicity. Furthermore, PAF can modulate the production of both interleukin 1 and interleukin 2 (IL-1, IL-2) from rat monocytes and lymphocytes, respectively [222, 223], cytokines which in turn elicit the release of other mediators and growth factors. 

Tumour necrosis factor (TNF) was originally described as a factor produced following exposure of Bacille-Calmette-Guerin-treated animals to bacterial endotoxin. It was so named because it possessed the ability to necrotise tumours. This factor is now named TNF-a to distinguish it from another, related cytokine lymphotoxin, which is sometimes referred to as TNF-/J Alternative names for TNF-a include cachectin and cytotoxin. Its primary cellular source in the body is the activated macrophage, but some other cell types (e.g. NK cells, astrocytes, some lymphocytes, fibroblasts, many tumour cells, endothelial cells and neutrophils) have also been shown to synthesise this cytokine. 

Figure 18.5 A summary of the biochemical, physiological and immunological changes brought about by cytokines in response to trauma. Cytokines can be produced in trauma from macrophages, lymphocytes, endothelial cells in the tissue that is damaged, and also by Kupffer cells if the liver is damaged. IL-1, IL-6 - interleukins 1 and 6 TNF - tumour necrosis factor, IFN - interferon.

The proinflammatory cytokines (interleukins 1 and 6 and tumour necrosis factor alpha) from macrophages are raised in depression. This leads to increased PGE2 synthesis and release which may lead to a reduction in central monoamine release. 

Almost 20 years ago the ammonium tellnrolate AS 101 was demonstrated to possess immnnomodnlating properties and to mediate anti-tumour effects in rats. The same com-ponnd stimnlates hnman lymphoid cells to proliferate and produce lymphokines, tumour necrosis factor (TNF) and other cytokines in vitro ... 

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