Cytokine inflammation-associated

Tumor Necrosis Factor a TNF Receptor Associated Factors Cytokines Inflammation... 

It has been well documented that the anaemia of chronic disease, ACD, results in a lowering of various haematological parameters. Several mediators are involved, among them histamine, serotonin, bradykinin, prostaglandins and, as found more recently, cytokines and nitric oxide. ACD is a parameter of systemic autoimmune disorders. The severe inflammatory stimuli lead to several systemic changes, mediated by inflammation-associated cytokines, e.g. IL-6, IL-1 TNFa, TGF beta that regulate hepatic synthesis of the acute phase proteins. 

Colchicine, an alkaloid obtained from the autumn crocus, has long been used and is relatively selective for the treatment of acute gouty arthritis. Unlike many of the newer agents for use in gout, colchicine has minimal effects on uric acid synthesis and excretion it decreases inflammation associated with this disorder. It is thought that colchicine somehow prevents the release of the chemotactic factors and/or inflammatory cytokines from the neutrophils, and this in turn decreases the attraction of more neutrophils into the affected area (Fig. 37.1).The ability of colchicine to bind to leukocyte microtubules in a reversible covalent complex and cause their depolymerization also may be a factor in decreasing the attraction of the motile leukocytes into the inflamed area. 

ThEF-a (tumour necrosis factor alpha) is the best known member of a group of pro-inflammatory cytokines, including interleukin-1 (IL-1) and interleukin-6 (IL-6), collectively responsible for the fever and inflammation associated with infections and serious disease. 

Potential therapeutic benefits of antioxidants to reduce intracellular oxidative stress have not yet been evaluated in vasculific neuropathy associated w ith autoimmune disease. Such anti-oxidants as vitamin E, a-lipoic acid or benfotiamine may be effective in interrupting the pro-inflammatory transcription factors and subsequent NF-[kappa]B regulated cytokines that initiate and maintain inflammation associated w ith vasculific neuropathy (Haselbeck et al., 2004). 

These changes are induced by a complex intercellular signalling system, whose main constituents are inflammation-associated cytokines. Among other functions. Interleukin-1, Interieukin-6 and Tumour Necrosis Factor-a initiate the alteration of protein and amino acid metabolism designed to support the increased demand of amino acids to sustain the immune response. In particular, lnterleukin-6, stimulates the production of hepatic APP. The relationship with the sulphurated amino acids (SAA) will be discussed in the following chapters. 

CosgroveBD, KingBM, Hasan MA, etal. Synergistic drug-cytokine induction of hepatocellular death as an in vitro approach for the study of inflammation-associated idiosyncratic drug hepatotoxicity. Toxicol Appl Pharmacol. 2009 237(3) 317-330. 

A variety of molecules including mediators generated during the immune response to tumours are also known as important factors for the progression of cancer, especially inflammation-associated cancer. Proinflammatory cytokines such as interleukin-6 (1L-6) and tumour necrosis factor (TNF) have significant roles in inflammation-associated cancer [62], Several lines of evidence indicate that IL-6 promotes tumour growth both in vitro and in vivo [17, 103], whereas TNF is known to have both anti- and pro-cancer actions [12], TNF can induce... 

Ben-Baruch, A. 2006. Inflammation-associated immune suppression in cancer the roles played by cytokines, chemokines and additional mediators. Semin Cancer Biol 16 38. 

Baughman et al. (72) also studied the changes in BAL IL-8 over time in patients with ARDS who were part of a study of surfactant replacement therapy. In 28 comparison patients who were not treated with surfactant replacement, the IL-8 concentration at the onset of ARDS was similar to that reported in other studies (median = 1186 pg/mL). The IL-8 concentration at the beginning of ARDS did not separate patients who lived or died. In survivors the IL-8 concentration fell between days 1 and 4, whereas in patients who died the IL-8 concentrations increased. This study did not confirm the value of the IL-8 as a predictor of survival, but it did support the observation of Meduri et al. that a persistent increase in BAL IL-8 (and other cytokines) was associated with persistent pulmonary inflammation and a poor prognosis (71). 

Liver Fibrosis Liver fibrosis is a common end result of inflammation and/or necrosis. While the liver does have considerable regenerative capabilities, cytokine release associated with the inflammatory/necrotic process can lead to fibrosis that can have a deleterious effect on hepatic function, not only from the aspect of decreased hepatic functional mass but also from the standpoint of compromising blood supply. Animal models of hepatic fibrosis would be valuable from the standpoint of facilitating the development of noninvasive biomarkers as well as development of interventional agents. 

The involvement of NK cells in the removal of damaged cells or cells that have lost self recognizing surface receptors in periprosthetic tissues has not been investigated. Like the Th17 cells, NK cells secrete cytokines that regulate T and B cell responses, and they are involved in the development of autoimmune diseases. Finally, the disregu-lation of Treg cells may also affect the tissue response to wear debris by failure to suppress the activity of stimulated immune cells. The involvement of T cell subsets and NK cells in periprosthetic tissue inflammation associated with UHMWPE wear debris will require additional studies. 

It is synthesized from 1-arginine by nitric oxide synthase (NOS) (Moncada et al. 1991). There are two classes of NOS, constitutive NOS (neural type and endothelial type) and inducible NOS (iNOS). Generally, neural NOS and endothelial NOS, whieh are known to generate NO at low concentrations, are expressed constitutively in neurons and endothelial cells, respectively, and their activity depends on elevated intraeytoplasmic calcium/calmodulin levels. On the other hand, iNOS, which generates large amounts of NO for prolonged periods of time, is produced by neutrophils, macrophages, epithelial cells, and many other cell types, and induction of it requires bacterial products or inflammation-associated cytokines independent of calcium/calmodulin concentration (Nathan and Xie 1994 Knowles and Moncada 1994). 

Inflammatory disorders are due to hyperactivity of leukocytes and overexpression of their associated integrins, cytokines, and chemokines, which leads to various disorders including arthritis, bowel diseases and other chronic inflammations. 

The inflammatory response in UC is propagated by atypical type 2 helper T cells that produce proinflammatory cytokines such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor (TNF).7 As discussed previously, a genetic predisposition to UC may partially explain the development of excessive colonic and rectal inflammation. The finding of positive perinuclear antineutrophil cytoplasmic antibodies (pANCA) in association with the human leukocyte antigen (HLA)-DR2 allele in a large percentage of patients with UC supports this theory.4,12... 

Agents targeting the excessive immune response or cytokines involved in IBD are potential treatment options (Table 16-3). Azathioprine and its active metabolite 6-mercaptopurine (6-MP) are inhibitors of purine biosynthesis and reduce IBD-associated GI inflammation. They are most useful for maintaining remission of IBD or reducing the need for long-term use of corticosteroids. Use in active disease is limited by their slow onset of action, which may be as long as 3 to 12 months. Adverse effects associated with azathioprine and 6-MP include hypersensitivity reactions resulting in pancreatitis, fever, rash, hepatitis, and leukopenia.25,26... 

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