Immune system Tumor necrosis factor

Human tumor necrosis factor (TNF) (Fig. 1) is a hormone-like proinflammatory peptide belonging to the group of cytokines. It is mainly produced by cells of the immune system in response to infection, inflammation, or cell damage. Disregulated TNF is an important factor in many pathological situations, like sqDsis, rheumatoid arthritis, inflammatory bowel disease (Crohn s disease), and Cachexia. The cytotoxic activity of TNF is of interest in development of new antitumoral strategies. 

TNF. Tumor necrosis factor. TNFs are among the important cytokines playing a key role in activation and induction of some immune system cells and cellular immunity processes responsible for proinflammatory and inflammatory response reactions as well. 

Ahn SY, Cho CH, Park KG, Lee HI, Lee S, Park SK, Lee IK, Koh GY (2004) Tumor necrosis factor-alpha induces fractaUdne expression preferentially in arterial endothelial cells and mithramycin A suppresses TNF-alpha-induced fractaUdne expression. Am J Pathol 164 1663-1672 Alfano M, Schmidtmayerova H, Amelia CA, Pushkarsky T, Bukrinsky M (1999) The B-oligomer of pertussis toxin deactivates CC chemokine receptor 5 and blocks entry of M-tropic HIV-1 strains, [see comments]. J Exp Med 190 597-605 Ambrosini E, Alois F (2004) Chemokines and glial cells a complex network in the central nervous system. [Review] [239 refs]. Neurochem Res 29 1017-1038 Azuma Y, Ohura K (2002) Endomorphins 1 and 2 inhibit IL-10 and IL-12 production and innate immune functions, and potentiate NE-kappaB DNA binding in THP-1 differentiated to macrophagelike cells. Scand J Immunol 56 260-269... 

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-... 

Neutrophils, lymphocytes, and monocytes are attracted to the area, and monocytes are converted to macrophages.18,19 The macrophages then stimulate additional prostaglandin production. Phagocytic cells and other players in the immune system release cytokines, including interleukins, interferon, and tumor necrosis factor. 

Other Factors. ECT no doubt destroys the homeostasis of the cancerous cells by profoundly disturbing their microenvironment and by dismantling their structure. It might also lead to the inhibition of their DNA synthesis. It has been speculated that ECT might release the Tumor Necrosis Factor (TNF) or, somehow super-activate the immune system at the tumor site. 

The LF is the most disruptive to cellular functions and disables intracellular signaling molecules. It prevents macrophages from releasing tumor necrosis factor (TNF) and interleukin cytokines, although the production of TNF and cytokines in the macrophages is not impeded. The host s immune system is compromised and is unable to eliminate the anthrax bacillus. 

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. 

Some new materials perspective for advanced biomedical technologies, especially carbon nanoparticles like fullerenes, are potentially mutagenic, carcinogenic and immunogenic [16,65], Therefore, standard tests of the morphological transformation of Syrian hamster embryonic cells in cultures on these materials (described in detail by [68,69]) can be performed. Immune activation of bone and vascular cells on the materials can be estimated by increased concentration of immunoglobulin and selectin adhesion molecules (ICAM-1, VCAM-1, ELAM-1), which bind cells of the immune system [15,16,18,19,23], as well as by the production of cytokines, such as tumor necrosis factor alpha or interleukins beta [55],... 

Cytokines are proteins that serve as signal molecules in cell-cell communication, and as such, perform a central and very diverse function in growth and differentiation of an organism. Representatives of cytokines control proliferation, differentiation and function of cells of the immune system and of cells of the blood-forming system. Furthermore, they are involved in processes of inflammation and in the neuronal, hema-poetic and embryonal development of the organism. Known cytokines include the interleukins (IL), erythropoietin, growth hormone, interferons (INF) and tumor necrosis factor (TNF) (see Table 8.1). A review of cytokines and cytokine receptors is to be found in HiU and Treisman, (1995) Taniguchi et al., (1995) and Moutoussamy et al., (1998). 

Fig. 11.1. Principle of an immunological synapse. Possibilities for communication between B and T cells during an immune response. Antigenic peptides are presented by the MHC complex class II at the surface of the B cell. The antigens are recognized and bound by T cell receptors of the T cell. The T cell receptor is activated and sets a signal chain in motion that leads to activation of the expression of cytokines, such as IL-2. The cytokine is secreted, and binds and activates a cytokine receptor on the B cell. TNFa is shown as another example of a ligand-receptor system. TNFa communicates, as a membrane-bound ligand, with a corresponding receptor on the surface of the B cell. The interactions shown take place in a narrow spatial region between B and T cells, which is why this system is referred to as an immunological synapse. TNF tumor necrosis factor MHC major histocompatibility complex IL-2 interleukin 2.

The pathogenesis of alcoholic liver disease is a multifactorial process involving metabolic repercussions of ethanol oxidation in the liver, dysregulation of fatty acid oxidation and synthesis, and activation of the innate immune system by a combination of direct effects of ethanol and its metabolites and by bacterial endotoxins that access the liver as a result of ethanol-induced changes in the intestinal tract. Tumor necrosis factor- , a proinflammatory cytokine that is consistently... 

Anti-TNF antibodies, eg, infliximab, others Bind tumor necrosis factor and prevent it from binding to its receptors Suppression of several aspects of immune function, especially ThI lymphocytes Infliximab Moderately severe to severe Crohn s disease and ulcerative colitis others approved in Crohn s disease Infusion reactions reactivation of latent tuberculosis increased risk of dangerous systemic fungal and bacterial infections... 

The effect of echinacea on the immune system is controversial. In vivo human studies using commercially marketed formulations of E purpurea have shown increased phagocytosis, total circulating white blood cells, monocytes, neutrophils, and natural killer cells but not immunostimulation. In vitro, Epurpurea juice increased production of interleukins-1, -6, and -10, and tumor necrosis factor- by human macrophages. Enhanced natural killer cell activity and antibody-dependent cellular toxicity was also observed with E purpurea extract in cell lines from both healthy and immunocompromised patients. Studies using the isolated purified polysaccharides from Epurpurea have also shown cytokine activation. Polysaccharides by themselves, however, are unlikely to accurately reproduce the activity of the entire extract. 

Endotoxicity results from the interaction of a bacterial cell envelope component (e.g., LPS or PG with a cell surface receptor constituting part of the nonspecific immune system, (i.e., a toll-like receptor on white blood cells). This results in the production of cytokines [e.g., interleukin 1 (IL-1) or tumor necrosis factor (TNF)] as part of an intracellular enzyme cascade which can cause severe tissue injury. Bioassays or immunoassays can be used to detect such reactions respectively. As noted above the most widely used bioassay is the LAL assay. A lysate of amoebo-cytes of the horseshoe crab (Limulus) contains an enzymatic clotting cascade which is activated by extremely low levels of LPS (nanogram levels or lower). There are variants of this assay that can detect PG, but they are not as widely used. As noted above, other bioassays employ cultured cell lines that respond to LPS or PG, respectively. Unfortunately bioassays are highly amenable to false positives (from the presence of cross-reactive substances) or false negatives from inhibition (by contaminants present in the sample) [10]. A detailed discussion of these assays is beyond the scope of this chapter and has been reviewed elsewhere [1]. 

Cytokines are a heterogenous group of polypeptide mediators that have been associated with activation of numerous functions, including the immune system and inflammatory responses. The cytokine families include, but are not limited to, interleukins, chemokines, tumor necrosis factors, interferons (INF-a, -0, and -y), colony-stimulating factors, growth factors, neuropoietins, and neurotrophins (see Table 13.4). 

Finally, in addition to the issues of costs and secondary events, treatment is also lacking for many more at-risk patients who cannot undergo successful angioplasty. These patients, who may have either diffuse, nonstentable, bifurcated lesions, or multivessel disease (i.e., diabetics), are not benefiting as much from DES, and improved treatments here also remain a clear clinical need. Often there is a systemic and local activation of the immune response, followed by a consequent local vascular incident. The role of the systemic immune response in these individuals, as well as in cardiovascular patients in general, is evidenced by the numerous reports of correlation of disease with increases in plasma markers such as CRB tumor necrosis factor, and even circulating white cell counts (87-89). 

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