title: Tetrathiomolybdate is effective in a mouse model of arthritis.
abstract: OBJECTIVE
  To test for protective effects of therapy with tetrathiomolybdate, a copper-lowering drug, against collagen-induced arthritis in mice.
  
  
  METHODS
  Mice were injected with bovine collagen II, and limb joint swelling and erythema were scored. Tetrathiomolybdate treated mice received drug by oral gavage or in drinking water. Plasma ceruloplasmin was followed as a measure of body copper status, and maintained between 20 and 60% of baseline. Urine for isoprostane studies was collected in metabolic cages. At sacrifice, blood was collected for cytokine assays, and hind limbs fixed in formalin.
  
  
  RESULTS
  Tetrathiomolybdate strongly protected against the collagen-induced arthritis as reflected in scores of swelling and erythema, and as seen histologically. Further, tetrathiomolybdate strongly protected against the increase in urine isoprostanes (a marker of oxidant damage) seen in collagen treated controls. The drug also protected against the increase in interleukin 2, interleukin 1beta, and tumor necrosis factor-a levels seen in collagen treated controls.
  
  
  CONCLUSIONS
  Based on the positive results reported here, and the good safety profile of tetrathiomolybdate in human studies so far, a trial of tetrathiomolybdate in arthritis syndromes seems warranted.
authors.affiliation: Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109-0534, USA.
authors.forename: Mark D
authors.initials: MD
authors.lastname: McCubbin
authors.forename: Guoqing
authors.initials: G
authors.lastname: Hou
authors.forename: Gerald D
authors.initials: GD
authors.lastname: Abrams
authors.forename: Robert
authors.initials: R
authors.lastname: Dick
authors.forename: Zhan
authors.initials: Z
authors.lastname: Zhang
authors.forename: George J
authors.initials: GJ
authors.lastname: Brewer
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002570:Ceruloplasmin / Q000032:analysis; D002614:Chelating Agents / Q000627:therapeutic use*; D003300:Copper / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D004487:Edema / Q000188:drug therapy / Q000473:pathology; D004890:Erythema / Q000188:drug therapy / Q000473:pathology; D028421:Isoprostanes / Q000652:urine; D007596:Joints / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008982:Molybdenum / Q000627:therapeutic use*; D016896:Treatment Outcome; D014881:Water Supply
chemical_list: D018501:Antirheumatic Agents; D002614:Chelating Agents; D016207:Cytokines; D028421:Isoprostanes; D003300:Copper; D008982:Molybdenum; C020809:tetrathiomolybdate; D002570:Ceruloplasmin