Summaries of the chapters

Rat adjuvant (AA) and collagen-induced (CIA) polyarthritis models, and more recently the monoarticular streptococcal cell wall (SCW) model have been used to evaluate novel therapeutic approaches to treat Rheumatoid Arthritis. All three models share mechanistic and pathologic features with each other, as well as with human RA. Most notably, they are all T cell and macrophage mediated. All have been linked to pro-inflammatory molecules, and exhibit elevations in serum acute phase proteins. Differences in joint destruction, cytokine and inflammatory mediator production and paw edema between the animal models are mostly quantitative, not qualitative. As a general rule, the AA model is the most robust, followed by CIA and then SCW. However, the aggressive nature of all of these animal models needs to be considered when comparing to human RA. The AA model has been the most extensively used, thereby having the largest database, which aids in predicting potential human efficacy, and its robust nature allows for ease in compound evaluation and ranking. CIA has an advantage due to the auto-antibody component and the directed nature of the cartilage destruction. The SCW model most closely resembles an arthritic flare, has fewer systemic complications, and requires much less compound when given therapeutically. In this review, we will compare these three animal models by discussing paw swelling and its associated joint histopathology, gene expression in joints, as well as acute phase proteins and biomarkers of cartilage and bone integrity, in addition to imaging technologies to quantify bone destruction.