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Experimental Biology and Medicine 2003-Jan

Dietary conjugated linoleic acid decreased cachexia, macrophage tumor necrosis factor-alpha production, and modifies splenocyte cytokines production.

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Mingder Yang
Mark E Cook

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The effect of conjugated linoleic acid (CLA) on macrophage functions were studied in vitro, in vivo, and ex vivo. In RAW macrophage cell line, CLA (mixed isomers) was shown to inhibit lipopolysaccharide (LPS)-stimulated tumor necrosis factor-alpha (TNF-alpha) production. Two CLA isomers, c9,t11 and t10,c12, were tested on RAW cells and it was found that the c9,t11 was the isomer responsible for the inhibition of LPS-induced TNF-alpha production. BALB/c mice were used to determine the effect of dietary CLA on body weight wasting and feed intake after LPS injection. CLA was protective against LPS-induced body weight wasting and anorexia. Plasma TNF-alpha levels after LPS injection were lower in the CLA group compared with the corn oil-fed control group 2 hr post-LPS injection. In a separate experiment, 30 mice were fed a CLA-supplemented diet or a corn oil-supplemented diet for 6 weeks and peritoneal resident macrophages were obtained for measuring TNF-alpha and nitric oxide production after in vitro exposure to interferon-gamma (IFN-gamma) and/or LPS. TNF-alpha production was not found to be different in peritoneal macrophages from mice fed the dietary treatments, but less nitric oxide was produced in macrophages from CLA-fed mice upon stimulation when compared with macrophages from control-fed mice. Splenocytes were also collected from the mice fed the dietary treatments and stimulated to produce cytokines in culture. Supernatant was used to run cytokine enzyme-linked immunoabsorbant assays. Interleukin-4 (IL-4) was decreased in CLA-fed mice when splenocytes were stimulated with concanavalin A (Con A) for 44 hr; however, IL-2 and the IL-2-to-IL-4 ratio were elevated.

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