Tumor necrosis factor (TNF)-α is a critical inflammatory mediator of experimental autoimmune encephalomyelitis and multiple sclerosis, and may therefore be a useful target for immunotherapy. Therapeutic strategies aimed at TNF include pharmacological inhibitors of TNF synthesis and/or processing and biological inhibitors of TNF effects. Several anti-TNF agents are currently being tested in multiple sclerosis in pilot clinical trials.
9 Cleveland JL, Ihle JN. (1995) Contenders in FasL/TNF death signaling. Cell81: 479–482.
10.
10 Smith CA, Farrah T, Goodwin RG. (1994) The TNF receptor superfamily of cellular and viral proteins: Activation, costimulation, and death. Cell76: 959–962.
11.
11 Selmaj K et al. (1991) Identification of lymphotoxin and tumor necrosis factor in multiple sclerosis lesions. J Clin Invest87: 949–954.
12.
12 Cannella B, Raine CS. (1991) The adhesion molecule and cytokine prof ile of multiple sclerosis lesions. Ann Neurol37: 424–435.
13.
13 Brosnan CS, Selmaj K, Raine CS. (1988) Hypothesis: A role for tumor necrosis factor in immune-mediated demyelination and its relevance to multiple sclerosis. J Neuroimmunol18: 87–94.
14.
14 Selmaj KW, Raine CS. (1988) Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro. Ann Neurol23: 339–346.
15.
15 Selmaj K et al. (1991) Cytokine cytotoxicity against oligodendrocytes. Apoptosis induced by lymphotoxin. J Immunol147: 522–529.
16.
16 Powell MB et al. (1990) Lymphotoxin and tumor necrosis factor-alpha production by myelin basic protein-specific T cell clones correlates with encephalitogenicity. Int Immunol2: 540–544.
17.
17 Ruddle NH et al. (1990) An antibody to lymphotoxin and tumor necrosis factor prevents transfer of experimental allergic encephalomyelitis. J Exp Med172: 193–200.
19 Beck J et al. (1988) Increased production of interferon gamma and tumor necrosis factor precedes clinical manifestation in multiple sclerosis: Do cytokines trigger off exacerbations? Act Neurol Scand78: 318–323.
20.
20 Sharief MK, Hentges R. (1991) Association between tumor necrosis factor-α and disease progression in patients with multiple sclerosis. N Engl J Med325: 467–472.
21.
21 Rudick RA, Ransohoff RM. (1992) Cytokine secretion by multiple sclerosis monocytes. Relationship to disease activity. Arch Neurol49: 265–270.
22.
22 Chofflon M et al. (1992) Tumor necrosis factor a production as a possible predictor of relapse in patients with multiple sclerosis. Eur Cytokine Netw3: 523–531.
23.
23 Imamura K et al. (1993) Cytokine production by peripheral blood monocytes/macrophages in multiple sclerosis patients. Acta Neurol Scand87: 281–265.
24.
24 Reickmann P et al. (1994) Cytokine mRNA levels in mononuclear blood cells from patients with multiple sclerosis. Neurology44: 1523–1526.
25.
25 Spuler S et al. (1996) Multiple sclerosis: Prospective analysis of TNF-α and 55kD TNF receptor in CSF and serum in correlation with clinical and MRI activity.J Neuroimmunol, in press.
26.
26 Zipp F et al. (1995) Genetic control of multiple sclerosis: Increased production of lymphotoxin and tumor necrosis factor-alpha by antigen-specific T cell lines from HLA-DR2 positive individualsAnn Neurol38: 723–730.
27.
27 Myers LW et al. (1995) Pentoxifylline not a promising treatment for multiple sclerosis. Neurology45 (Suppl. 4): A419.
28.
28 Sinha B et al. (1995) Enhanced tumor necrosis factor suppression and cyclic monophosphate accumulation by combination of phosphodiesterase inhibitors and prostanoids. Eur J Immunol25: 147–153.
29.
29 Sommer N et al. (1995) The antidepressant rolipram suppresses cytokine production and prevents autoimmune encephalomyelitis. Nature Med1: 244–248.
30.
30 Genain CP et al. (1995) Prevention of autoimmune demyelination in non-human primates by a cAMP-specific phosphodiesterase inhibitor. Proc Natl Acad Sci USA92: 3601–3605.
31.
31 Lee JC et al. (1994) A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature372: 739–746.
32.
32 Scheinman RI et al. (1995) Role of transcriptional activation of IkBα in mediation of immunosuppression by glucocorticosteroids. Science270: 283–286.
33.
33 Auphan N et al. (1995) Immunosuppression by glucocorticoids: Inhibition of NF-kB activity through induction of IkB synthesis. Science270: 286–290.
34.
34 Gearing AJH et al. (1994) Processing of tumor necrosis factor-α precursor by metalloproteinases. Nature370: 555–557.
35.
35 McGeehan GM et al. (1994) Regulation of tumour necrosiss factor-α processing by a metalloptoteinase inhibitor. Nature370: 558–561.
36.
36 Mohler KM et al. (1994) Protection against a lethal dose of endotoxin by an inhibitor of tumor necrosis factor processing. Nature370: 218–220.
37.
37 Baker D et al. (1994) Control of established allergic encephalomyelitis by inhibition of tumour necrosis factor (TNF) activity within the central nervous system using monoclonal antibodies and TNF-receptor-immunoglobulin fusion proteins. Eur J Immunol24: 2040–2048.
38.
38 Selmaj K et al. (1995) Prevention of chronic relapsing experimental autoimmune encephalomyelitis by soluble tumor necrosis factor receptor I. Neuroimmunol56: 135–141.
39.
39 Elliott MJ et al. (1994) Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor-α (cA2) versus placebo in rheumatoid arthritis. Lancet344: 1105–1110.
40.
40 Elliott MJ et al. (1994) Repeated therapy with monoclonal antibody to tumour necrosis factor α (cA2) in patients with rheumatoid arthritis. Lancet344: 1125–1127.
