| Title | Treatment of collagen induced arthritis in DBA/1 mice with L-asparaginase. | | Author(s) | Reiff A, Zastrow M, Sun BC, Takei S, Mitsuhada H, Bernstein B, Durden DL | | Institution | Division of Rheumatology, Childrens Hospital Los Angeles, California 90027, USA. reiff@hsc.usc.edu | | Source | Clin Exp Rheumatol 2001 Nov-Dec; 19(6):639-46. | | MeSH | Animals
Antineoplastic Agents
Arthritis, Experimental
Arthrography
Asparaginase
Dose-Response Relationship, Drug
Drug Combinations
Escherichia coli
Joints
Lipopolysaccharides
Male
Mice
Mice, Inbred DBA
Polyethylene Glycols
Research Support, Non-U.S. Gov't
Treatment Outcome
| | Abstract | OBJECTIVE: To evaluate the safety and efficacy of L-asparaginase as an immunosuppressive agent in a mouse model of rheumatoid arthritis.
METHODS: Male DBA/1 mice with collagen-induced arthritis (CIA) were treated at different intervals with various doses of native and pegylated L-asparaginase from E. coli. The mice were observed for 4 weeks during which time arthritis was scored. Outcome parameters included effect on severity and progression of established arthritis as well as prevention of disease. In addition, X-rays from the affected joints were obtained for comparison.
RESULTS: Both native L-asparaginase at a dose of 50 IU/injection intraperitoneally three days a week and pegylated asparaginase (PEG-L-asparaginase) at a dose of 25 IU/injection twice a week, significantly reduced the mean arthritic score (MAS) in mice with established arthritis (p < 0.001 for PEG-L-asparaginase). When native L-asparaginase was administered before the onset of arthritis (days 14-post immunization) the number of mice developing arthritis as well as the number of arthritic paws and the severity of arthritis in the treatment group were significantly decreased (p < 0.0001). Significant differences were found in the X-ray evaluation between treated and control mice. None of the animals died due to drug related events or showed signs of asparaginase induced toxicity.
CONCLUSION: Our data provide the first direct evidence that L-asparaginase is a potent antiarthritic agent and may represent an effective second line agent for future treatment studies in juvenile and adult rheumatoid arthritis. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 11791634 |
|
