Multiple sclerosis tumor necrosis factor

Feldmann, M. et al. (1997). Anti-tumor necrosis factor-a therapy of rheumatoid arthritis. Adv. Immunol. 64, 283-350. Hohlfeld, R. (1997). Biotechnological agents for the immunotherapy of multiple sclerosis — principles, problems and... 

While the specific mechanisms of action of interferon-pia and interferon-pib in MS are not fully understood, each interferon has a number of immune-mediating activities (see Section 7.1). A recent review article on multiple sclerosis observed The interferons reduce the proliferation of T cells and the production of tumor necrosis factor a, decrease antigen presentation, alter cytokine production to favor ones governed by type 2 helper T (Th2) cells, increase the secretion of interleukin-10, and reduce the passage of immune cells across the blood-brain barrier by means of their effects on adhesion molecules, chemokines, and proteases [2]. 

Beck J, Rondot P, Catinot L, Falcot E, Kir diner H, Wietzerbin J (1988) Increased production of interferon gamma and tumor-necrosis factor precedes clinical manifestation in multiple sclerosis Do cytokines trigger off exacerbations Acta Neurol Scand 78 318-323. 

Hofman FM, Hinton DR, Johnson K, Merrill JE (1989) Tumor necrosis factor identified in multiple sclerosis brain. J Exp Med 170 607-612. 

Strunk T, Bubel S, Mascher B, Schlenke P, Kirchner H, Wandinger KP (2000) Increased numbers of CCR5-I- interferon-gamma- and tumor necrosis factor-alpha-secreting T lymphocytes in multiple sclerosis patients. Ann Neurol 47 269-273. 

Mikova O, Yakimova R, Bosmans E, Kenis G, Maes M (2001) Increased serum tumor necrosis factor alpha concentrations in major depression and multiple sclerosis. Eur Neuropsychophar-macol 11 203-208. 

Two remarkable successes of cytokine therapy are the treatment of multiple sclerosis with interferon-p and the treatment of rheumatoid arthritis and inflammatory bowel disease with tumor necrosis factor-a inhibitors. 

Robinson WH, Genovese MC, Moreland LW. Demyelinating and neurologic events reported in association with tumor necrosis factor alpha antagonism by what mechanisms could tumor necrosis factor alpha antagonists improve rheumatoid arthritis but exacerbate multiple sclerosis Arthritis Rheum 2001 44(9) 1977-83. 

The authors speculated that the most likely explanation for these observations was linked to the lack of transfer of high-molecular weight soluble receptors and IgG across the blood-brain barrier, implying that control of brain tumor necrosis factor alfa cannot be obtained with monoclonal antibodies. They thought that neurological complications in diseases other than multiple sclerosis might be related to control of tumor necrosis factor alfa in the periphery, resulting in an enhanced contribution of brain-derived tumor necrosis factor alfa or other cytokines, such as interleukin-1. 

Selmaj, J., Raine, C. S., Cannella, B., and Brosnan, C. F., Identification of lymphotoxin and tumor necrosis factor in multiple sclerosis lesions, J. Clin. Invest., 87, 949, 1991b. 

SPMS secondary-progressive multiple sclerosis SSPE subacute sclerosing panencephalitis TGF-/S transforming growth factor /3 TLI total lymphoid irradiation TNF-a tumor necrosis factor alpha WHO World Health Organization... 

Sharief MK, Thompson El. In vivo relationship of tumor necrosis factor alpha to blood-brain barrier damage in patients with active multiple sclerosis. I Neuroiimnunol 1992 38 27-33. 

F31. Fugger, L., Morling, N., Sandberg Wollheim, M., Ryder, L. P., and Svejgaard, A. Tumor necrosis factor alpha gene polymorphism in multiple sclerosis and optic neuritis. J. Neuroimmunol. 27, 85-88 (1990). 

H9. Hauser, S. L., Doolittle, T. H., Lincoln, R., Brown, R. H., and Dinarello, C. A. Cytokine accumulations in CSF of multiple sclerosis patients Frequent detection of interleukin-1 and tumor necrosis factor but not interleukin-6. Neurology 40, 1735-1739 (1990). 

Franciotta, D. M., Grimaldi, L. M. E., Martino, G. V., Piccolo, G., Bergamaschi, R., Citterio, A., and Melzi-d Eril, G. V. (1989). Tumor necrosis factor in serum and cerebrospinal fluid of patients with multiple sclerosis. Ann. Neurol. 26, 787-789. 

Sharief, M. K., and Hentges, R. (1991). Association between tumor necrosis factor-Q and disease progression in patients with multiple sclerosis. N. Engl. J. Med. 325, 467-472. 

Second, the concentration at 4 pM 3-sitosterol (44) could reduce the tumor necrosis factor-a (TNFa) release by 24% in the peripheral blood mononuclear cells of the multiple sclerosis patients, whereas 10 j,M simvastatin (45) of a lipid-lowering drug could reduce the tumor necrosis factor-a (TNFa) release by 94%. P-sitosterol (44) at the concentration of 4 and 16 j,M could reduce the interleukin-12 (IL-12) release in the multiple sclerosis patients by 27% and 30%, respectively. 

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