Tumor necrosis factor interleukin-10 inhibition

Becher B, Dodelet V, Fedorowicz V, Antel IP (1996) Soluble tumor necrosis factor receptor inhibits interleukin 12 production by stimulated human adult microglial cells in vitro. J Clin Invest 98 1539-1543. 

K. R. Feingold, W. Doereler, C.A. Di-narello, W. Fiers, and C. Gruneeld, Stimulation of lipolysis in cultured fat cells by tumor necrosis factor, interleukin-1, and the interferons is blocked by inhibition of prostaglandin synthesis, Endocrinology, 1992, 130, 10-16. 

Many patients with liver failure have a malabsorption syndrome and chronic diarrhea. Chronic diarrhea causes zinc deficiency because stool contains substantial quantities of zinc. Cytokines such as tumor necrosis factor, interleukin-1, and interleukin-6 may stimulate metal-lothionein, an intestinal zinc-binding protein, thereby inhibiting zinc absorption. Considering the importance of zinc in metalloenzyme reactions, wound healing, immunocompetence, and the senses of taste and smell, patients with chronic diarrhea or large ostomy losses should be suspected of having zinc deficiency measurement of serum concentrations may be used to confirm such deficiencies. Patients receiving a protein-restricted diet may be at additional risk because substantial amounts of zinc are found in red meat. 

D19. Dinarello, C. A., Okusawa, S., and Gelfland, J. A., Interleukin-1 induces a shock-like state in rabbits Synergism with tumor necrosis factor and the effect of cyclooxygenase inhibition. In Molecular and Cellular Mechanisms of Septic Shock. Alan R. Liss, New York, 243-263... 

P16. van der Poll, T., Coyle, S. M., Barbosa, K., Braxton, C. C., and Lowry, S. F., Epinephrine inhibits tumor necrosis factor-alpha and potentiates interleukin-10 production during human en-dotoxemia. J. Clin. Invest. 97,713-719 (1996). 

The ability of natural products to inhibition of topoisomerase and precipitate apoptosis mentioned in this chapter are two abilities among several others, of which inhibition of microtubule formation, inhibition of DNA polymerase, protein kinases, protein phosphatase and aromatase, and the use of cytokines, interleukins, and tumor necrosis factor and yet uncovered cellular targets. 

Ohlsson, B.C., Englund, M.C., Karlsson, A.L., Knutsen, E., Erixon, C, Skribeck, H., Liu, Y., Bondjers, G., and Wiklund, O., 1996, Oxidized low density lipoprotein inhibits hpopolysaccharide-induced binding of nuclear factor-kappaB to DNA and the subsequent expression of tumor necrosis factor-alpha and interleukin-1 beta in macrophages, J. Clin. Invest. 98 78-89. 

Anti-hepatitis B virus activity in vitro and in vivo was also found in wogonin and baicalein (Fig. 4), the major active constituents of the traditional Chinese medicine Scutellaria radix.More recently, Blach-Olszewska et al investigated the effect of baicalein and wogonin on two important mechanisms of innate immunity The secretion of cytokines, and the natural resistance of human leukocytes to viral infection. The results obtained indicate that these fiavonoids modulate cytokine production, that is they inhibit interferons-a and -y, and stimulate tumor necrosis factor-a and interleukin production. They also augment the resistance of peripheral blood leukocytes to the vesicular stomatitis virus. 

Thalidomide (Thalomid) is a derivative of glutamic acid that is chemically related to glutethimide. It exerts a number of biological effects as an immunosuppressive, antiinflammatory, and antiangiogenic agent, yet its mechanisms of action have not been fuUy elucidated. Thalidomide potently inhibits production of tumor necrosis factor (TNF) a and interleukin (IL) 12, and its effect on these and other cytokines may account for some of its clinical effects. 

Cyclosporine can bind to the cytosolic protein cy-tophilin C. This drug-protein complex inhibits cal-cineurin phosphatase activity, which leads to a decreased synthesis and release of several cytokines, including interleukins IL-2, IL-3, IL-4, interferon-a, and tumor necrosis factor. 

Southern, C., Schulster, D., and Green, 1. C. (1990). Inhibition of insulin secretion by interleukin-1/3 and tumor necrosis factor-a via an L-arginine-dependent nitric oxide generation mechanism. FEBS Lett. 276, 42-44. 

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]. 

Inflammation is now recognized as a key process in atherogenesis [Libby, 2002]. The potential for dietary flavonoids to inhibit inflammatory activities is of particular interest. A potential anti-inflammatory feature of the flavonoids is the ability to inhibit the biosynthesis of eicosanoids. Selected phenolic acids and some flavonoids have been shown to inhibit both cyclooxygenase (COX) and 5-lipoxygenase (5-LO) pathways [Nijveldt et al., 2001 Takano-Ishikawa et al., 2006], Epicatechin and related flavonoids have been shown to inhibit the synthesis of pro-inflammatory cytokines in vitro [Sanbongi et al., 1997], and plasma metabolites of catechin and quercetin inhibit the adhesion of monocytes to cultured endothelial cells [Koga and Meydani, 2001]. Silymarin has been shown to inhibit the production of inflammatory cytokines, such as interleukin-1, interferon-, and tumor necrosis factor-a (TNFa), from macrophages and T-cells [Matsuda et al., 2005], Some flavonoids can inhibit neutrophil... 

The expression of iNOS and the generation of NO in LPS-activated RAW 264.7 cells were inhibited by resveratrol [Murakami et al., 2003 Tsai et al., 1999], The compound significantly diminished the expression of tumor necrosis factor (TNF)-o mRNA in LPS-activated J774.2 macrophage cells [Kowalski et al., 2005] and peripheral blood leukocytes [Richard et al., 2005]. The expression of interleukin (IL)-8 protein and/or its mRNA in human monocytic leukemia (U937) cells [Shen et al., 2003] and human peripheral blood... 

In addition to direct effects on genes regulating inflammation, glucocorticoids also inhibit the transcription factors that initiate synthesis of pro-inflammatory cytokines (e.g., interleukin-1, tumor necrosis factor), enzymes (e.g., COX-2, nitric oxide synthase), and receptor proteins (e.g., natural killer receptors).17,87,89 Glucocorticoids may also exert some of their effects via a membrane-bound receptor that regulates activity of macrophages, eosinophils, T lymphocytes, and several other types of cells involved in the inflammatory response.89 Consequently, glucocorticoids affect many aspects of inflammation, and their powerful anti-inflammatory effects in rheumatoid arthritis result from their ability to blunt various cellular and chemical components of the inflammatory response. 

TCDD inhibits the terminal differentiation of B cells via alteration of an early activation event, perhaps increased protein phosphorylation and tyrosine kinase activity (Clark et al. 1991a Kramer et al. 1987 Luster et al. 1988 Morris et al. 1991). Macrophage functions, examined ex vivo, generally have been found to be resistant to suppression by 2,3,7,8-TCDD (Mantovani et al. 1980 Vos et al. 1978). There is also evidence suggesting that inflammatory cells may be activated by 2,3,7,8-TCDD via enhanced production of inflammatory mediators such as interleukin 1 and tumor necrosis factor (Clark et al. 1991b Taylor etal. 1992). 

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