TNF function

Inhibition of TNF function through modulation of its signal transduction pathways Inhibition of TNF Production and Secretion... 

CrmB Variola Secreted Human, mouse, rat TNF human LTa and chemokines Blocks human, mouse and rat TNF function 47... 

CrmB Monkeypox secreted Human, mouse and rabbit TNF Blocks human, mouse and rabbit TNF function 48... 

CrmC Cowpox Secreted (late gene) Human and mouse TNF Blocks human and mouse TNF function 43... 

CrmE Cowpox Secreted Human, mouse and Rat TNF Blocks human TNF function 45... 

M-T2 Myxoma Secreted (early gene) Rabbit TNF human TNFR Blocks rabbit TNF, human TNF function 12,55... 

TPV-2L Tanapox Secreted (early) Human, monkey, canine and rabbit TNF Blocks human, monkey and canine TNF function 38,39... 

YMTV-2L Yabamonkey secreted tumor virus Human, monkey and rabbit TNF Blocks human and monkey TNF function 39... 

In some cases, poxvirus-encoded vTNFR homologues have additional properties in addition to the binding and inhibiting of TNF functions. This has been demonstrated in case of myxoma virus encoded M-T2 protein, which has a second anti-apoptotic role. In case of CrmE, it has recendy been shown that the protein also possesses chcmokinc binding properties. Thus, un-hke the engineered commercial TNF inhibitors currendy used in humans, the virus-encoded modulators sometime possess addidonal anti-inflammatory properties above and beyond just TNF inhibition. 

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). 

Clinically, GM-CSF or G-CSF have been used to accelerate recovery after chemotherapy and total body or extended field irradiation, situations that cause neutropenia and decreased platelets, and possibly lead to fatal septic infection or diffuse hemorrhage, respectively. G-CSF and GM-CSF reproducibly decrease the period of granulocytopenia, the number of infectious episodes, and the length of hospitalization in such patients (152), although it is not clear that dose escalation of the cytotoxic agent and increased cure rate can be rehably achieved. One aspect of the effects of G-CSF and GM-CSF is that these agents can activate mature cells to function more efficiently. This may, however, also lead to the production of cytokines, such as TNF- a, that have some toxic side effects. In general, both cytokines are reasonably well tolerated. The side effect profile of G-CSF is more favorable than that of GM-CSF. Medullary bone pain is the only common toxicity. 

TNF is a pleiotropic cytokine exerting a wide range of cellular responses, that affect biological processes such as lipid metabolism, coagulation, and insulin resistance and the function of endothelial cells. As a major proinflammatory cytokine TNF is also involved in progression of diseases like cancer, Alzheimer, Diabetes type II, cardiovascular, pulmonary or neurological disorders, and many autoimmune diseases. Blocking the action of TNF clearly reduces its inflammatory potential on various autoimmune disorders like Crohn s disease, rheumatoid arthritis (RA), and psoriasis. 

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... 

TNF activates inflammatory functions of various immune cells, not only as a direct effector but also as part of the cytokine network (synergism with IL-1, IFN-y, and LPS), as shown in Table 2 (K11). TNF interacts with the complement system and induces the additional release of eicosanoids. TNF has many effects on... 

Interleukin-10 (IL-10) affects antigen presentation capacity but also interferes with many other functions of monocytes and macrophages (Table 2) (F8). In vitro, IL-10 is a potent inhibitor of cytokine production, including production of TNF, IL-1, IL-6, and IL-8 by LPS-activated monocytes/macrophages (F8). It also inhibits tissue factor-dependent procoagulant activity induced by LPS in human... 

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