Tumor necrosis factor effects

Santana, P., Llanes, L., Hernandez, I., Gallardo, G., Quintana, J., Gonzalez, J., Estevez, F., Ruiz de Galarreta, C., and Fanjul, L. F. (1995). Ceramide mediates tumor necrosis factor effects on P450-aromatase activity in cultured granulosa cells. Endocrinology 136, 2345-2348. 

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. 

For additional evaluation of the effect of hydrophobization and the molecular weight of the polymers on the biological immuno-stimulating activity, we investigated the ex vivo cytokine (interIeukin-6 [IL-6], and tumor necrosis factor [TNFj-inducing activity from human peripheral whole blood cells of hydrophobized polymers by use of fractionated poly(M A-CDA) with narrow poly-dispersity. Since this assay uses the intact human cells, it shows more accurate results than in vitro assay using cultured cell line [25]. 

Cytokines and biological response modifiers represent a broad class of therapeutic agents that modify the hosts response to cancer or cancer therapies. The enormous body information about their clinical uses and their side effects is beyond the scope of this essay that can only give illustrative examples. For an up-to-date information the reader can resort to reference [5]. As many as 33 different interleukins are known and the list continues to grow IL-2 used in the treatment of kidney cancer is one example. Interferon alpha is used for chronic myelogenous leukeia, hairy cell leukaemia and Kaposi s sarcoma. Interferons are also used in the treatment of chronic infections such as viral hepatitis. Tumor necrosis factor (alpha), G/GM/M-CSF, and several other cellular factors are used in treatment of various cancers. Many of these cytokines produce serious side effects that limit their use. 

Fig. 14 Effect of the molecular weight of tamarind seed xyloglucan depolymerized by ( ) 7-irradiation, ( ) ultrasonication, and ( ) endo-glucanase treatment on the production of various cytokines (Tumor necrosis factor a, TNE-a Interleukin 8, IL-8 Interleukin 10, IL-10 and Interleukin 12, IL-12) in HaCaT cells (Immortalized keratinocytes line) [301]...

Biber K, Zuurman MW, Dijkstra IM, Boddeke HW (2002) Chemokines in the brain neuroimmunology and beyond. Curr Opin Pharmacol 2 63-68 Blasko 1, Veerhuis R, Stampfer-Kountchev M, Saurwein-Teissl M, Eikelenboom P, Grubeck-Loebenstein B (2000) Costimulatory effects of interferon-gamma and interleukin-1 beta or tumor necrosis factor alpha on the synthesis of Abetal-40 and Abetal-42 by human astrocytes. Neurobiol Dis 7 682-689... 

Selective inhibition of tumor necrosis factor-induced vascular cell adhesion molecule-1 gene expression by a novel flavonoid. Lack of effect on trascriptional factor NF-kB Arteriosclerosis, Thrombosis and Vascular Biology 16, 1501-8. 

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-... 

Etanercept is a recombinant form of human tumor necrosis factor receptor.24 Etanercept provides a therapeutic effect by binding to soluble TNF and preventing its binding with TNF receptors. It is administered subcutaneously once or twice weekly noticeable symptomatic improvement is seen in 1 to... 

B21. Bertini, R., Bianchi, M., and Ghezzi, P Adrenalectomy sensitizes mice to the lethal effects of interleukin 1 and tumor necrosis factor. J. Exp. Med 167,1708-1712 (1988). 

B23. Beutler, B., Milsark, I. W., and Cerami, A., Passive immunization against cachectin/tumor necrosis factor protects mice from the lethal effects of endotoxin. Science 229,869-871 (1985)... 

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... 

F12. Flores, E. A., Bistrian, B. R., Pomposelli, J. J., Dinarello, C. A., Blackburn, G. L, and Istfan, N. W., Infusion of tumor necrosis factor/cachectin promotes muscle catabolism in the rat. A synergistic effect with interleukin l.J. Clin. Invest. 83, 1614-1622 (1989). 

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). 

Z8. Zuckerman, S. H., Shellhaas, J., and Butler, L. D., Differential regulation of lipopolysaccharide-induced interleukin I and tumor necrosis factor synthesis Effects of endogenous and exogenous glucocorticoids and the role of the pituitary-adrenal axis. Eur. J. Immunol. 19,301-305 (1989). 

Browning, J., and Ribolini, A. (1989) Studies on the differing effects of tumor necrosis factor and lym-photoxin on the growth of several human tumor lines./. Immunol. 143, 1859-1867. 

Louise CB, Obrig TG Shiga toxin-associated hemolytic-uremic syndrome Combined cytotoxic effects of Shiga toxin, interleukin-1 beta, and tumor necrosis factor alpha on human vascular endothelial cells in vitro. Infect Immun 1991 59 4173-4179. 

Morimoto, Y., Z. Nambu, I. Tanaka, T. Higashi, H. Yamato, H. Hori, S. Cho, and M. Kido. 1995. Effects of nickel oxide on the production of tumor necrosis factor by alveolar macrophages of rats. Biol. Trace Elem. Res. 48 287-296. 

Walsh BW, Cox DA, Sashegyi A, Dean RA, Tracy RP, Anderson PW (2001) Role of tumor necrosis factor-alpha and interleukin-6 in the effects of hormone replacement... 

Mohan, V.P. et al., Effects of tumor necrosis factor alpha on host immune response in chronic persistent tuberculosis Possible role for limiting pathology, Infect. Immun., 69, 1847, 2001. 

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. 

Moos, A., Oughton, J., and Kerkvliet, N.I., The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on tumor necrosis factor (TNF) production by peritoneal cells, Toxicol. Lett., 90, 145,1997. 

---