Investigation of the role of tumour necrosis factor-α, interleukin-1β, interleukin-10, nitric oxide and rheumatoid factor-immunoglobulin M in a rat model of arthritis

Abstract

Collagen-induced arthritis (CIA) in rats is a widely used preclinical animal model of rheumatoid arthritis (RA). However, CIA development in Sprague-Dawley (SD) rats is less severe in terms of inflammatory response compared with other strains. Therefore, a modified CIA model called MCIA, using N-acetylmuramyl dipeptide (MDP), has been developed in the less sensitive SD rat strains. This work was conducted to better understand the immunopathological role and contributions of the pro-inflammatory T-helper type 1 (Th-1) cytokines and inflammatory mediators, interleukin-1 (IL-1beta), tumour necrosis factor-alpha (TNF-alpha) and nitric oxide (NO); the anti-inflammatory T-helper type 2 (Th-2) cytokine, IL-10 and autoantibodies such as rheumatoid factor (RF)-immunoglobulin M (IgM) in this newly developed RA model. TNF-alpha, NO and RF-IgM levels were significantly increased, while IL-1beta levels were not affected in this MCIA rat model. The levels of IL-10 were lower than the baseline when compared with controls. (1) the immunological features represented in the MCIA rat model favour the Th-1 cytokine profile over Th-2 and (2) RF-IgM can be used as a diagnostic test in preclinical RA models.