Rodent Preclinical Models for Developing Novel Antiarthritic Molecules: Comparative Biology and Preferred Methods for Evaluating Efficacy
Figure 2
Related rodent models of immune-mediated arthritis (RMIA) will respond in similar or different manners, depending upon the parameter being assessed. Rat adjuvant-induced arthritis initiated with lipoidal amine (AIA-LA) or heat-killed Mycobacterium tuberculosis H37Ra (AIA-Myc) develops 9 days after adjuvant injection. Both models exhibit similar declines in total body weight (a), increases in hind paw volume (b), and reductions in bone mineral density (BMD) in the knee (femorotibial joint) (c). However, BMD in the ankle (tibiotarsal and intertarsal) joints is reduced only in AIA-Myc (c). Another difference between the two models is the nature of the dose-response curve for inducing arthritis (d); the proinflammatory response to Mycobacterium H37Ra is linear across a broad dose range, while the response to lipoidal amine exhibits an abrupt threshold (at 50 mg/mL) below which adjuvant injection does not produce disease. Both AIA models were induced in young adult (7- to 8-week-old), male Lewis rats. Lipoidal amine was given as a single intradermal injection of 5 mg (in 0.1 mL of complete Freund's adjuvant; Difco Laboratories, Detroit, MI) at the tail base, while H37Ra was generated and administered as described in Section 6. Bars associated with data points represent standard error of the mean.
