Treatment of murine collagen-induced arthritis by ex vivo extracellular superoxide dismutase gene transfer

Arthritis Rheum. 2001 Sep;44(9):2160-7. doi: 10.1002/1529-0131(200109)44:9<2160::aid-art369>;2-0.


OBJECTIVE; Superoxide dismutase (SOD) is a potent antiinflammatory enzyme that has received growing attention for its therapeutic potential. This study was undertaken to examine the efficacy of extracellular SOD (EC-SOD) gene therapy in murine collagen-induced arthritis.

Methods: Embryonic DBA/1 mouse fibroblasts were infected with a recombinant retrovirus expressing human EC-SOD. DBA/1 mice that had been treated with type II collagen were administered subcutaneous injections of 2 x 10(7) EC-SOD-expressing fibroblasts on day 29, when symptoms of arthritis were already present. The severity of arthritis in individual mice was evaluated in a double-blind manner; each paw was assigned a separate clinical score, and hind paw thickness was measured with a caliper. Mice were killed on day 50 for histologic examination of the joints.

Results: High serum concentrations of EC-SOD were maintained for at least 7 days. Mice treated with the transgene exhibited significant suppression of clinical symptoms such as disabling joint swelling, deformity, and hind paw thickness, compared with the untreated group (mean +/- SD maximum clinical score in the untreated and the transgene-treated groups 2.71 +/- 1.08 and 1.35 +/- 1.22, respectively; P < 0.01, and hind paw thickness 3.04 +/- 0.18 mm and 2.56 +/- 0.12 mm, respectively; P < 0.05). Histologic abnormalities, including destruction of cartilage and bone, infiltration of mononuclear cells, and proliferation of synovial cells, were also markedly improved in the EC-SOD-treated mice compared with the control group (histopathologic score 7.50 +/- 1.13 and 4.13 +/- 1.88 in the untreated and transgene-treated groups, respectively; P < 0.05).

Conclusion: These results indicate that EC-SOD gene transfer may be an effective form of therapy for rheumatoid arthritis.

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / chemically induced
  • Arthritis, Rheumatoid / pathology
  • Arthritis, Rheumatoid / therapy*
  • Cells, Cultured
  • Collagen / pharmacology
  • Culture Media
  • Extracellular Space / enzymology
  • Female
  • Fibroblasts / cytology
  • Fibroblasts / enzymology
  • Gene Expression Regulation, Enzymologic
  • Genetic Therapy*
  • Hindlimb / pathology
  • Humans
  • Interleukin-1 / blood
  • Joints / pathology
  • Mice
  • Mice, Inbred DBA
  • Pregnancy
  • RNA, Messenger / analysis
  • Superoxide Dismutase / blood
  • Superoxide Dismutase / genetics*
  • Tumor Necrosis Factor-alpha / metabolism


  • Culture Media
  • Interleukin-1
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Collagen
  • Superoxide Dismutase