title: Anti-TNF-alpha antibody allows healing of joint damage in polyarthritic transgenic mice.
abstract: Anti-tumor-necrosis-factor-alpha (TNF-alpha) monoclonal antibody was used to treat Tg197 transgenic mice, which constitutively produce human TNF-alpha (hTNF-alpha) and develop a progressive polyarthritic disease. Treatment of both young (7- or 8-week-old) and aged (27- or 28-week-old) mice commenced when at least two limbs showed signs of moderate to severe arthritis. The therapeutic efficacy of anti-TNF-alpha antibody was assessed using various pathological indicators of disease progression. The clinical severity of arthritis in Tg197 mice was significantly reduced after anti-TNF-alpha treatment in comparison with saline-treated mice and in comparison with baseline assessments in both young and aged mice. The treatment with anti-TNF-alpha prevented loss of body weight. Inflammatory pathways as reflected by elevated circulating hTNF-alpha and local expression of various proinflammatory mediators were all diminished by anti-TNF-alpha treatment, confirming a critical role of hTNF-alpha in this model of progressive polyarthritis. More importantly, the amelioration of the disease was associated with reversal of existing structural damage, including synovitis and periosteal bone erosions evident on histology. Repair of cartilage was age dependent: reversal of cartilage degradation after anti-TNF-alpha treatment was observed in young mice but not in aged mice.
authors.affiliation: Centocor, Inc, Malvern, Pennsylvania, USA. dshealy@cntus.jnj.com
authors.forename: David J
authors.initials: DJ
authors.lastname: Shealy
authors.forename: Paul H
authors.initials: PH
authors.lastname: Wooley
authors.forename: Eva
authors.initials: E
authors.lastname: Emmell
authors.forename: Amy
authors.initials: A
authors.lastname: Volk
authors.forename: Amy
authors.initials: A
authors.lastname: Rosenberg
authors.forename: George
authors.initials: G
authors.lastname: Treacy
authors.forename: Carrie L
authors.initials: CL
authors.lastname: Wagner
authors.forename: Lois
authors.initials: L
authors.lastname: Mayton
authors.forename: Don E
authors.initials: DE
authors.lastname: Griswold
authors.forename: Xiao-Yu R
authors.initials: XY
authors.lastname: Song
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005542:Forearm / Q000473:pathology; D006579:Heterozygote; D006614:Hindlimb / Q000473:pathology; D007596:Joints / Q000187:drug effects / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D018925:Chemokines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha