Type-2 Collagen Monoclonal Antibody (mAB) Cocktail (CAIA)

Collagen antibody-induced arthritis (CAIA) is induced through the injection of a cocktail of anti-type II collagen monoclonal antibodies alone or in combination with LPS. LPS serves to ramp up the immune response sensitizing the animal to the type II collagen autoantibodies, producing a more robust and consistent induction of arthritic disease than with antibodies alone. The CAIA model, does not require the use of a strain with a particular MHC haplotype (such as DBA/1), and can be induced in most strains of mice. This model is ideal for studying the pathogenesis of rheumatoid arthritic disease, including the roles of different cytokines and the recruitment of inflammatory cells, and for evaluating the efficacy of novel test articles in a variety of different strains and genetic backgrounds.

Category(s)

Preclinical Drug Efficacy Studies

Species

Mice (Various strains can be used in this model)

Basic Methodology

Mice are injected i.v. with a cocktail of 4 monoclonal antibodies to type II collagen followed by an i.p. injection of LPS. Mice are scored for arthritis starting on Day 4 post-booster. Arthritis should develop on Day 4 and peak on Days 7-8. Therapeutic effects of test compounds can be determined on Day 7. Osteoblast formation and bone degradation should be more significant on Days 14-21. The administration of therapeutic compounds is performed according to the schedule set-forth in the study protocol.

Measurements

Clinical scoring of arthritis, body weight, hang-time (wire mesh), histopathology, cytokine profiling using ELISA and Luminex multiplex assays, and flow cytometric analysis for the characterization of inflammatory cell types

Reference Substance(s):

Dexamethasone

Literature References:

Woley, Paul (2008) What animal models are best to test novel rheumatoid arthritis therapies? Current Rheumatology Reviews; 4(4):1-11