title: Antibody-mediated inhibition of TNFR1 attenuates disease in a mouse model of multiple sclerosis.
abstract: Tumour necrosis factor (TNF) is a proinflammatory cytokine that is known to regulate inflammation in a number of autoimmune diseases, including multiple sclerosis (MS). Although targeting of TNF in models of MS has been successful, the pathological role of TNF in MS remains unclear due to clinical trials where the non-selective inhibition of TNF resulted in exacerbated disease. Subsequent experiments have indicated that this may have resulted from the divergent effects of the two TNF receptors, TNFR1 and TNFR2. Here we show that the selective targeting of TNFR1 with an antagonistic antibody ameliorates symptoms of the most common animal model of MS, experimental autoimmune encephalomyelitis (EAE), when given following both a prophylactic and therapeutic treatment regime. Our results demonstrate that antagonistic TNFR1-specific antibodies may represent a therapeutic approach for the treatment of MS in the future.
authors.affiliation: Department of Neuro-oncology, University Clinic Heidelberg, Heidelberg, Germany.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Williams
authors.affiliation: Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Maier
authors.affiliation: Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, Germany.
authors.forename: Roman
authors.initials: R
authors.lastname: Fischer
authors.affiliation: Department of Neuro-oncology, University Clinic Heidelberg, Heidelberg, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Fairless
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: Sonja
authors.initials: S
authors.lastname: Hochmeister
authors.affiliation: Department of Neuro-oncology, University Clinic Heidelberg, Heidelberg, Germany.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Stojic
authors.affiliation: Department of Neurology, University of the Saarland, Homburg/Saar, Germany.
authors.forename: Lara
authors.initials: L
authors.lastname: Pick
authors.affiliation: Department of Neurology, University of the Saarland, Homburg/Saar, Germany.
authors.forename: Doreen
authors.initials: D
authors.lastname: Haar
authors.affiliation: Department of Neurology, University of the Saarland, Homburg/Saar, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Musiol
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: Maria K
authors.initials: MK
authors.lastname: Storch
authors.affiliation: Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Pfizenmaier
authors.affiliation: Department of Neuro-oncology, University Clinic Heidelberg, Heidelberg, Germany.
authors.forename: Ricarda
authors.initials: R
authors.lastname: Diem
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D005260:Female; D015870:Gene Expression; D007167:Immunotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058990:Molecular Targeted Therapy; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000235:genetics; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics
chemical_list: D000906:Antibodies; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; C506236:Tnfrsf1a protein, mouse