title: Reduction of arthritis and pneumonitis in motheaten mice by soluble tumor necrosis factor receptor.
abstract: OBJECTIVE
  To determine the effects of anti-tumor necrosis factor (anti-TNF) therapy in the inflammatory and autoimmune disease in motheaten (me/me) mice, which exhibit a Fas apoptosis signaling defect.
  
  
  METHODS
  Arthritis, pneumonitis, and mortality were analyzed in me/me mice treated with a novel, soluble, dimeric TNF receptor I (sTNFRI) molecule capable of high-affinity binding and neutralization of TNFalpha.
  
  
  RESULTS
  Soluble TNFRI reduced serum levels of TNFalpha and led to a 2-fold increase in the lifespan of me/me mice, compared with the control treatment group. The treatment also reduced the development of the "motheaten" skin patches and alleviated pneumonitis and inflammatory lesions in the extremities of me/me mice compared with controls. However, the serum levels of IgM and IgM anti-double-stranded DNA autoantibody were comparable to those of untreated control mice.
  
  
  CONCLUSIONS
  TNFalpha is an important cytokine involved in the pathogenesis of inflammatory disease in me/me mice, resulting in tissue damage and early mortality. Therapies directed at blocking TNF/TNFR interactions, such as the sTNFRI used in these experiments, may be effective in diseases associated with apoptosis defects leading to overutilization of the TNF/TNFR pathway.
authors.affiliation: The University of Alabama at Birmingham, 35294-0007, USA.
authors.forename: X
authors.initials: X
authors.lastname: Su
authors.forename: T
authors.initials: T
authors.lastname: Zhou
authors.forename: P
authors.initials: P
authors.lastname: Yang
authors.forename: C K
authors.initials: CK
authors.lastname: Edwards
authors.forename: J D
authors.initials: JD
authors.lastname: Mountz
mesh_terms: D000505:Alopecia / Q000188:drug therapy; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D001168:Arthritis / Q000188:drug therapy* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D001667:Binding, Competitive / Q000276:immunology; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D019281:Dimerization; D008136:Longevity; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D009154:Mutation; D011014:Pneumonia / Q000188:drug therapy* / Q000276:immunology; D011092:Polyethylene Glycols; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I; D011994:Recombinant Proteins / Q000494:pharmacology; D016019:Survival Analysis; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D001323:Autoantibodies; D002352:Carrier Proteins; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D011994:Recombinant Proteins; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha; C069521:recombinant human tumor necrosis factor-binding protein-1; D011092:Polyethylene Glycols