Conjugated linoleic acid (CLA) prolongs the survival and reduces cachexia of the autoimmune NZB/W F1 mouse: Role of cytokine regulation by CLA in body weight wasting and murine systemic lupus erythematosus

Conjugated linoleic acids (CLA) are a mixture of naturally occurring 18 carbon diene fatty acids with double bonds in an uninterrupted position. The positional and geometrical configuration of the conjugated dienes result in biological properties distinct from its parent compound, linoleic acid (18:2, c9,c12).; We have hypothesized that CLA's immune enhancing activity would exacerbate autoimmune disease. Autoimmune NZB/W F1 mice, a well-established murine model for study human systemic lupus erythematosus, were fed a control diet or 0.5% CLA and the progression of disease was studied. When CLA was fed immediately after weanling, autoimmunity and proteinuria appeared earlier, but survival post proteinuria was extended 1.5 fold in CLA fed mice versus control. Life was also prolonged 1.7 fold over control fed mice when CLA was fed post proteinuria. Body weight wasting, associated with the end stage lupus erythematosus, was decreased in CLA-fed mice.; Prolonged survival and anti-cachectic effects of CLA led to a hypothesis that CLA alters cytokine production in immune cells. Studies were conducted to determine CLA's role on the cachectic cytokine TNF-α as well as II-2, II-4 productions in non-autoimmune mice. CLA was found to decrease plasma TNF-α post endotoxin injection in BALB/c mice when compared to corn oil fed mice. Macrophages cultured with the c9,t11 isomer of CLA had decreased TNF-α production when challenged with endotoxin and compared to linoleic acid treated cells. Splenocytes from CLA fed mice, when compared to corn oil fed mice, had higher IL-2 and lower IL-4 production following IFN-γ/endotoxin exposure. Data in non-autoimmune mice provide one possible mechanism by which CLA prolongs life and prevents cachexia in the autoimmune NZB/W F1 mouse.