Evaluation of therapeutic targets in animal models of arthritis: How does it relate to rheumatoid arthritis?

Abstract

Introduction Rheumatoid arthritis (RA) is a chronic, systemic, immune-mediated inflammatory disease associated with decreased life expectancy and quality of life. RA is characterized by chronic inflammation and synovial hyperplasia leading to destruction of cartilage and bone. A better understanding of the pathophysiology of RA has led to significant improvements in its treatment. However, many questions remain with respect to the pathogenesis of RA, and disease remission is achieved in only a minority of patients. Therefore, there is still a need to develop novel antirheumatic therapies. Animal models of RA complement descriptive studies of well-defined patient samples and in vitro studies and represent important tools for the development and evaluation of new treatment options. This review article addresses the immunologic characteristics of and similarities and differences between a variety of animal models of human RA. Commonly used animal models such as collagen-induced arthritis (CIA), adjuvant-induced arthritis (AIA), and a model of spontaneous arthritis using tumor necrosis factor (TNF)–transgenic mice are described. We also discuss the less frequently used models of streptococcal cell wall (SCW)–induced arthritis, proteoglycan-induced arthritis (PGIA), and K/BxN-transgenic mice, including the serum transfer–induced (STIA) model, to indicate the variety of animal models with specific characteristics that are available and that could be used to study specific components and stages of the inflammation process. Furthermore, we describe the effects of some targeted interventions, comparing animal studies with clinical trials. Finally, the importance of choosing a suitable animal model of arthritis for screening the preclinical efficacy of newly developed therapeutics is addressed.