Inflammatory tumor necrosis factor

Cytokines and Immunophilins. A large number of inflammatory mediators and related proteins including the cytokines, colony stimulating factors (CSFs), interferons (IFNs), tumor necrosis factors (TNFs), growth factors (see Growth regulators), neurotrophic factors, and immunophilins are found in the mammalian CNS and appear to play a significant role in CNS function both in development and in aspects of brain homeostasis (40—43). 

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. 

Other pro-inflammatory factors produced and secreted by these cell populations snch as interlenkins (IL) -1, -6, -12, and tumor necrosis factor alpha (TNF-a) are instrnmental in the resolution of bacterial clearance (Daley et al. 2005 Ishikawa and Miyazak 2005 Kudo et al. 2005 Man et al. 2007 Wang et al. 2005 Warner and Srinivasan 2004). 

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-... 

Inflammatory cytokines have been implicated in the pathophysiology of HF.9 Several proinflammatory (e.g., tumor necrosis factor-a [TNF-a], interleukin-1, interleukin-6, and interferon-y) and anti-inflammatory cytokines (e.g., interleukin-10) are overexpressed in the failing heart. The most is known about TNF-a, a pleiotrophic cytokine that acts as a negative inotrope, stimulates cardiac cell apoptosis, uncouples 3-adrenergic receptors from adenylyl cyclase, and is related to cardiac cachexia. The exact role of cytokines and inflammation in HF pathophysiology continues to be studied. 

Eosinophils may be increased in some patients, particularly during exacerbations. Activated inflammatory cells release a variety of mediators, most notably leukotriene B4, interleukin-8, and tumor necrosis factor-a (TNF-a). Various proteinases, such as elastase, cathepsin G, and proteinase-3, are secreted by activated neutrophils. These mediators and proteinases are capable of sustaining inflammation and damaging lung structures. 

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... 

Activated T cells begin releasing cytokines including interleukin-2 (IL-2), interferon-y, (IFN-y), tumor necrosis factor (TNF-a), and others.4,13 Cytokine activity leads to a rapid proliferation and turnover of skin cells, triggering the inflammatory process and the development of psoriatic skin lesions.4,13,14 TNF-a may have a role in disease severity it upregulates endothelial and keratinocyte expression of ICAM-1,... 

Multiple factors play a role in the development of AOM. Viral infection of the nasopharynx impairs eustachian tube function and causes mucosal inflammation, impairing mucociliary clearance and promoting bacterial proliferation and infection. Children are predisposed to AOM because their eustachian tubes are shorter, more flaccid, and more horizontal than adults, which make them less functional for drainage and protection of the middle ear from bacterial entry. Clinical signs and symptoms of AOM are the result of host immune response and damage to cells caused by inflammatory mediators such as tumor necrosis factor and interleukins that are released from bacteria.4... 

P17. van der Poll, T., Levi, M Van Deventer, S. J., Ten Cate, H., Haagmans, B. L., Biemond, B. J., Buller, H. R Hack, C. E., and Ten Cate, J. W., Differential effects of anti-tumor necrosis factor monoclonal antibodies on systemic inflammatory responses in experimental endotoxemia in chimpanzees. Blood 83,446-451 (1994). 

Local inflammatory changes occur in the joint capsule and synovium. The synovium becomes infiltrated with T cells, and immune complexes appear. Crystals or cartilage shards in synovial fluid may contribute to inflammation. There are also increased levels of interleukin-1, prostaglandin E2, tumor necrosis factor-a, and nitric oxide in synovial fluid. Inflammatory changes result in effusions and synovial thickening. 

The most common etiology is exposure to environmental tobacco smoke, but other chronic inhalational exposures can also lead to COPD. Inhalation of noxious particles and gases stimulates the activation of neutrophils, macrophages, and CD8+ lymphocytes, which release a variety of chemical mediators, including tumor necrosis factor-a, interleukin-8, and leukotriene B4. These inflammatory cells and mediators lead to widespread destructive changes in the airways, pulmonary vasculature, and lung parenchyma. 

Tumor necrosis factor a (TNF-a) is a multifunctional cytokine produced by activated monocytes-macrophages. TNF-a is one of the most potent osteoclastogenic cytokines produced in inflammation, and, in addition, TNF-a induces IL-1 synthesis. Like the other known stimulators of bone resorption, it acts through osteoblastic cells however, it has been demonstrated that TNF-a is able to induce osteoclast formation from stromal-depleted macrophages, with potency similar to that of RANKL (Kobayashi et al. 2000). TNF-a is able to induce bone resorption in vitro (Thomson et al. 1987) as well as in vivo (Koning et al. 1988). Osteoclasts induced by TNF-a have the capacity to form resorption pits on dentine slices only in the presence of IL-la. TNF-a, together with IL-1, plays an important role in bone resorption in inflammatory diseases (Kobayashi et al. 2000). Inhibition of TNF by TNF binding protein (TNFbp) completely prevents bone loss and osteoclast formation (Kimble et al. 1997). 

Gardner, C.R. et al., Exaggerated hepatotoxicity of acetaminophen in mice lacking tumor necrosis factor receptor-1. Potential role of inflammatory mediators, Toxicol. Appl. Pharmacol., 192, 119, 2003. 

Early research showed that Pb exposure could increase sensitivity to bacterially-derived endotoxins [63] as well as increase production of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-a) by macrophages [64-67], Studies in several species indicate that Pb boosts production of TNF-a both immediately following adult exposure and in later life following gestational exposure. Flohe and coworkers [67] reported that Pb-induced elevation in TNF-a production is sensitive to both protein kinase C signaling as well as protein production. Not only can the production of TNF-a be elevated following exposure to Pb, but also the expression of the receptor for TNF-a (TNF-R) is elevated [68], Therefore, the combined effect of elevated cytokine production by macrophages as well as increased receptor expression would be expected to contribute to problematic inflammatory responses. 

---