TNF

Cytokines, eg, interferons, interleukins, tumor necrosis factor (TNF), and certain growth factors, could have antitumor activity directiy, or may modulate cellular mechanisms of antitumor activity (2). Cytokines may be used to influence the proliferation and differentiation of T-ceUs, B-ceUs, macrophage—monocyte, myeloid, or other hematopoietic cells. Alternatively, the induction of interferon release may represent an important approach for synthetic—medicinal chemistry, to search for effective antiinflammatory and antifibrotic agents. Inducers of interferon release may also be useful for lepromatous leprosy and chronic granulomatous disease. The potential cytokine and cytokine-related therapeutic approaches to treatment of disease are summarized in Table 4. A combination of cytokines is a feasible modaUty for treatment of immunologically related diseases however, there are dangers inherent in such an approach, as shown by the induction of lethal disserninated intravascular coagulation in mice adrninistered TNF-a and IFN-y. 

Ah = Antibody IL = interleukin TNF =tumornecrosis factor INF = interferon LAK =lymphocyte-activated killer CSF =colony stimulating factors and FGF = fibroblast growth factor. 

Mono-, di-, and trivalent bromides and iodides may be made by methods similar to the chlorides. The lower valence salts also disproportionate in water. Indium trifluoride [7783-52-0] InF., is sparingly soluble in water. It forms an ammonium double salt, SNH F TnF. [15273-84-4] which decomposes on heating to indium nitride [25617-98-5] InN. 

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). 

The intrinsic charge-generation efficiency of polymers is often low and needs to be enhanced by the addition of sensitizers. The sensitizer can be dissolved in the polymer to enhance the bulk charge-generation efficiency of the polymer. Effective sensitizers include 2,4,7-trinitro-9- uorenone [129-79-3] (TNF), hiUerene, thiapyryhum dye, CdS nanoclusters, etc (Table 3). Molecular stmctures of selected sensitizers are shown in Figure 8. 

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. 

A critical step in radioprotection involves the IL-1 receptors. Monoclonal antibodies to the type 1 IL-1 receptor block IL-l-induced radioprotection (167). Although this receptor is not present on BM cells, it is present on fibroblasts, which suggests that the effects of IL-1 on stem cells maybe largely indirect and mediated by stromal cell activation (168). Anti-IL-1 receptor (type 1) also sensitizes normal mice to the effects of TBI, which suggests that endogenous IL-1 has an intrinsic radioprotective role. IL-6 induction by IL-1, but not CSF levels, is inhibited, which supports the concept that G-CSF and GM-CSF are insufficient by themselves at radioprotecting stem cells and indicates a contributory role for IL-6. Anti-IL-6 antibody blocks IL-1 and TNF-induced radioprotection and also decreases the intrinsic radioresistance of mice, as does anti-TNF- a (169). 

Anti-SCF antibody similarly abrogates Hpopolysaccharide- and IL-l-induced radioprotection (170) and sensitized mice to radiation. Such effects are not obtained using anti-IL-3, anti-IL-4, or anti-GM-CSF antibodies. SCF, IL-1, IL-6, and TNF- a have acknowledged interactive roles in the normal... 

Clinical use of lL-1, lL-6, and TNF- a, is limited by associated systemic toxicity. SCF seems better tolerated. It may be possible to develop derivatives of other cytokiaes that are less toxic. The synthetic nonapeptide VQGEESNDK (position 163—171 of human lL-1 P) (see Amino acids ... 

TNF.I. - Idaho National Engineering Laboratory, PSA analysts and research, insolation - Heating (of a plume) by the sun. 

Phthalimides with a-TNF production regulating activity as novel biological response modifiers (a-TNF is a-tumor necrotic factor) 97YZ91. 

The ex vivo IL-6 and TNF-inducing activities of fractionated and modified or unmodified poly(MA-CDA) were performed according to the method reported [26] and shown in Figs. 12 and 13, respectively. A similar tendency was shown in IL-6 and TNF induction from peripheral whole blood cells by those of poIy(M A-CDA). 

Figure 13 TNF inducing activity of poly(MA-CDA)s from human peripheral whole blood cell culture. The doses of poly(MA-CDA)s were I mg/ml and 100 /ng/ml. The doses of the LPS were 10 and 1 ng/ml.

Vascular Endothelial Growth Inhibitor (Protein sharing homology with TNF-a) Inhibits EC proliferation... 

Regional TNF-a therapy Isolated limb perfusion to target in transit metastases... 

LTB4, PGE2) PAF, histamine, IL-1, IL-6, IL-8, tNF-oc, MCP Pain, edema, vasodilation, fever, leukocytosis... 

Anti-cytokines (e.g. IL-1, TNFs, IL-1 receptor constructs) Prostaglandins and PG mimetics... 

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