Autoimmune Prone Mice as a Model of Chronic Inflammation and Heart Disease

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Inflammation is a key component in the development of heart disease (Ross, 1999). The inflammatory process is propagated by immune cells like the T cell, which migrate to the site of inflammation. This is significant because the T cell plays a critical role in determining both the type and extent of immune response via the production of cytokines. Specifically, T cells have been shown to drive the inflammation found in atherosclerotic lesions (Benagiano et al., 2003). The inflammation in arterial walls is propagated by both the expression of adhesion molecules like ICAM-1 and VCAM-1, which recruit immune cells to the site of inflammation, and the production of cytokines by both nonimmune and immune cells. The autoimmune prone MRL-lpr has been used as an experimental system to examine chronic inflammation and heart disease (Qiao et al., 1993) primarily because many of the adhesion molecules and cytokines thought to be important in human atherosclerosis are up-regulated in this animal model.

Nutrients serve as an excellent means to delay the onset of heart disease (Osiecki, 2004). The omega-3 fatty acids found in fish oil are well-established anti-inflammatory nutrients (Fernandes and Jolly, 1998). Important in heart disease, dietary omega-3 fatty acids have been shown to suppress the expression of both ICAM-1 (De Caterina et al., 2000) and VCAM-1 (De Caterina et al., 1995) in endothelial cells. Proinflammatory cytokines like TNF-a and IFN-y are also found at sites of inflammation, and their levels can be reduced by dietary omega-3 fatty acid feeding in MRL-lpr mice (Venkatraman and Chu, 1999). We have specifically found that dietary omega-3 fatty acids can decrease IFN-y and TNF-a levels associated with nephritis in the kidneys of (NZBxNZW)F1 (B/W) mice. Furthermore, dietary omega-3 fatty acids have been shown to reduce IFN-y production in T-lymphocytes found in the peripheral blood, mesenteric lymph nodes, and spleens (Jolly, 2004) of B/W mice.

Omega-3 fatty acids can be derived from many food sources. Flaxseed oil, enriched in linolenic acid, and fish oil, enriched in eicosapentaenoic acid and docosahex-aenoic acid, are the two sources of omega-3 fatty acids that have been commonly used to examine the anti-inflammatory properties of omega-3 fatty acids. However, direct comparisons of the two oils are limiting in the literature. Recent evidence suggests that both flaxseed and fish oil could decrease T-lymphocyte proliferation ex vivo in rats, but fish oil was the most potent. Whether this translates into fish oil being the most effective at delaying the onset of heart disease and/or autoimmune disease needs to be directly addressed.

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