Animal rheumatoid arthritis

Metallic copper and silver both have antibacterial properties and Au thiol complexes have found increasing use in the treatment of rheumatoid arthritis, but only copper of this group has a biological role in sustaining life. It is widely distributed in the plant and animal worlds, and its redox chemistry is involved in a variety of... 

While the obvious value of in vivo animal models is clear, there also are instances—especially in cases of inflammatory arthritis, behavior, and tumor growth—where they have failed to be predictive of useful clinical activity in humans [51], For example, leukotriene (LTB4) antagonists showed activity in animal models of inflammatory arthritis yet failed to be useful in rheumatoid arthritis [52]. Similarly, dopamine D4 antagonists showed activity in animal behavior models previously predictive of dopamine D2 antagonists in schizophrenia. However, testing of dopamine D4 antagonists showed no efficacy in humans [53]. 

Anthony DD, Haqqi TM. Collagen-induced arthritis in mice an animal model to study the pathogenesis of rheumatoid arthritis. Clin Exp Rheumatol 1999 17(2) 240-244. 

Brahn E. Animal models of rheumatoid arthritis. Clues to etiology and treatment. Clin Orthop 1991(265) 42-53. 

Weekes J et al. Bovine dilated cardiomyopathy proteomic analysis of an animal model of human dilated cardiomyopathy Electrophoresis 1999 20 898-906. Doherty NS et al. Analysis of changes in acute phase plasma proteins in an acute inflammatory response and in rheumatoid arthritis using two-dimensional gel electrophoresis. Electrophoresis 1998 19 355-363. 

The most widely studied therapeutic proteins produced in plants include monoclonal antibodies for passive immunotherapy and antigens for use as oral vaccines [40]. Antibodies against dental caries, rheumatoid arthritis, cholera, E. coli diarrhea, malaria, certain cancers, Norwalk virus, HIV, rhinovirus, influenza, hepatitis B virus and herpes simplex virus have been produced in transgenic plants. However, the anti-Streptococcus mutans secretory antibody for the prevention of dental caries is the only plant-derived antibody currently in Phase II clinical trials [40]. Until recently, most antibodies were expressed in tobacco, potato, alfalfa, soybean, rice and wheat [9], It has been estimated that for every 170 tons of harvested tobacco, 100 tons represents harvested leaves. A single hectare could thus yield 50 kg of secretory IgA [3, 41]. Furthermore, it has been estimated that the cost of antibody production in plants is half that in transgenic animals and 20 times lower than in mammalian cell cul-... 

A number of studies in humans show that PUFAs can generate significant immunomodulatory effects. Generally, these studies have utilized considerably lower amounts of fish oil to treat subjects than found in most animal studies. Numerous clinical trials have examined the effects of fish oil on rheumatoid arthritis and many have reported statistically significant benefits such as decreased morning stiffness and numbers of tender joints [57]. Several other studies have reported that PUFAs can provide therapeutic benefits for patients with IgA nephropathy, the most common primary human glomerulonephritis... 

Cat K inhibitor therapy may also result in protection against the development of atherosclerosis. Cat K-deficient mice show reduced atherosclerotic lesion number and size on an ApoE receptor-deficient background, compared to wild-type animals [38,39]. Cat K is also associated with increased adiposity in humans [27,28] and may also play a role as a kininase, suggesting a role in blood pressure regulation [40]. Cat K has also been postulated to play a role in the pathology of rheumatoid arthritis [41,42],... 

The nonobese diabetic mouse (NOD), as well as the biobreeding (BB) rats are the two rodent models whose diabetes-related immunopathology is considered to be quite similar to that in humans. Studies in these animal models have revealed that autoreactive T cells that mediate islet 8 cell destruction belong to the Thl subset of T cells (produce IL-2 and IFN-7), whereas regulatory T cells are of the Th2 type (produce IL-4 and IL-10). Because Thl and Th2 cells are mutually inhibitory, there have been many trials using IL-4 and/or IL-10 for the prevention of autoimmune disease, like autoimmune diabetes, rheumatoid arthritis (Evans et al., 1996 Boyle et al., 1999), and inflammatory bowel disease (Rogy et al., 2000). 

Collagen-induced arthritis (CIA) in mice is an animal model for rheumatoid arthritis (RA) and can be induced in DBA/1 and C57BL/6 mice using different protocols. The CIA model can be used to unravel mechanisms involved in the development of arthritis and is frequently used to study the effect of new therapeutics. The development of a CIA model in C57BL/6 mice recently enabled researchers to use knockout mice on this background for arthritis research. 

Kannan, K., Ortmann, R. A. and Kimpel, D. (2005) Animal models of rheumatoid arthritis and their relevance to human disease. Pathophysiology 12, 167-181. 

Hegen, M., Keith, J. C., Jr., Collins, M. and Nickerson-Nutter, C. L. (2008) Utility of animal models for identification of potential therapeutics for rheumatoid arthritis. Ann Rheum )A67(11) 1505-1515. 

Young, D. A., Hegen, M., Ma, H. L., Whitters, M. J., Albert, L. M., Lowe, L., et al. (2007) Blockade of the interleukin-21/interleukin-21 receptor pathway ameliorates disease in animal models of rheumatoid arthritis. Arthritis Rheum 56, 1152-1163. 

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