Laboratory Animals > Laboratory Animals Online First > 10.1258/la.2009.0080132

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Original Article

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

M S Khalifeh ^1 3 , R Al-Rukibat ², W Hananeh ², A Boumezrag ¹ and O Okour ¹

¹ Department of Basic Veterinary Medical Science; ² Department of Veterinary Pathology and Animal Health, College of Veterinary Medicine, Jordan University of Science and Technology, PO Box 3030, Irbid 22110, Jordan; ³ Department of Molecular Biology and Genetic Engineering, Science College, Jordan University of Science and Technology, Irbid, Jordan

Corresponding author: M S Khalifeh. Email: mskn{at}just.edu.jo

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-1β), tumour necrosis factor-alpha (TNF-) 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-, NO and RF-IgM levels were significantly increased, while IL-1β levels were not affected in this MCIA rat model. The levels of IL-10 were lower than the baseline when compared with controls. In conclusion: (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.

Key Words: Collagen-induced arthritis • N-acetylmuramyl dipeptide • IL-1β • TNF- • IL-10 • rheumatoid factor-IgM • nitric oxide

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