Arthritis, Collagen mAb-Induced (CAIA)
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OVERVIEW
DOCUMENTS/REFERENCES
BIOLOGICAL INFORMATION
BACKGROUND INFORMATION
Classic collagen-induced arthritis (CIA), used as a model for rheumatoid arthritis, requires 6-8 weeks to complete a typical study in mice. Administration of a monoclonal antibody cocktail (mAbs) against type II collagen, however, can produce arthritis in mice within a few days. Further, severe and consistent arthritis can be induced in mice by a combination of a sub-arthritogenic dose of mAb cocktail and lipopolysaccharide (LPS). The hypothesis is that gastrointestinal absorbed bacterial toxin(s) play a synergistic and pathologic role with this type of treatment. Advantages of mAb-LPS-induced arthritis in mice as opposed to CIA include reduced time (days) and increased consistency (nearly 100%) of the inflammatory process.
ORGANISM
Mouse
ASSAY INFORMATION
ASSAY TYPE
In Vivo
TESTING INFORMATION
PROCEDURE SUMMARY
Groups of 6 male BALB/c mice weighing 22 ± 2 g are used. A combination of 5 different monoclonal antibodies (mABs: D8-6, F10-21, DI-2G, A2-10 and D2-112) is administered by intravenous injection (1.5 mg/mouse, IV) on Day 0 and challenged 3 days later (Day 3) with lipopolysaccharide (LPS, 25 μg/mouse, IV). From Day 3, beginning one-hour post LPS, vehicle and test article are administered orally (PO) once daily for 3 consecutive days. Arthritis is assessed by using a qualitative severity score system and hind paw volume (mL) measured with a plethysmometer on Days 5, 7, 10, 14 and 17. Additional analyses that can be requested include hind paw harvest and weight at termination, biomarkers (protein and/or mRNA) and histopathology etc. Suggested Testing: n=6/group (study design dependent). Doses may be administered PO, IV, IP and SC.
CRITERIA FOR SIGNIFICANCE
p<0.05 compared to vehicle control is considered significant activity
TURNAROUND TIME
STANDARD
30 Days
CLINICAL RELEVANCE
THERAPEUTIC AREA
Inflammation/Allergy
ADDITIONAL INFORMATION
BRAND
PDS
TESTING LOCATION
Taiwan - Taipei
OTHER INFORMATION
We will readily accommodate client-specified alterations. These studies are performed at our AAALAC accredited BSL-2 laboratory in Taipei, Taiwan. All aspects of this work are performed in general accordance with the Guide for the Care and Use of laboratory animals (National Academy Press, Washington, DC, 2011). The study protocol was approved by the Pharmacology Discovery Services IACUC and is performed with the oversight of veterinarians to assure the humane treatment of laboratory animals.
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