Tetrathiomolybdate is effective in a mouse model of arthritis.
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.
McCubbin
Mark D
MD
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109-0534, USA.
Hou
Guoqing
G
Abrams
Gerald D
GD
Dick
Robert
R
Zhang
Zhan
Z
Brewer
George J
GJ
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
D018501:Antirheumatic Agents; D002614:Chelating Agents; D016207:Cytokines; D028421:Isoprostanes; D003300:Copper; D008982:Molybdenum; C020809:tetrathiomolybdate; D002570:Ceruloplasmin