Generation of a robust model for inducing autoimmune arthritis in Sprague Dawley rats

Abstract

Introduction The prerequisite for any experimental model in animals is similarity with the human disease, uniformity in disease severity and incidence. In antigen-induced arthritis models it is generally recognized that the major limitation is inconsistency in terms of incidence and severity. As access to strains like DBA/1 mice or Lewis rats is difficult for resource restrained laboratories, this study aimed to establish a robust and reproducible animal model of rheumatoid arthritis (RA). Methods Multiple approaches were undertaken for inducing arthritis in Sprague Dawley (SD) and Wistar rats using complete Freund's adjuvant (CFA), collagen type II (CII) emulsion, or different combinations of CII with low dose CFA along with lipopolysaccharide (LPS). The development of arthritis was evaluated by measuring paw edema, arthritis score, body weight, splenic index, histopathology and radiography of paw tissues. Results The combination of CII with low dose CFA and one injection of LPS resulted in 100% incidence of arthritis with disease severity ranging from moderate to severe and results were corroborated by histopathology and radiography. Discussion In a head-to-head comparison between SD and Wistar rats, the disease profile was better sustained and consistent in SD rats, and the use of CII with low dose CFA and LPS induced features akin to human RA. Taken together, a reproducible model of arthritis was established which can be replicated in any laboratory with limited resources.