Fish oil alters T-lymphocyte proliferation and macrophage responses in Walker 256 tumor-bearing rats

Objective We investigated the effect of the dietary ratio of ω-6 to ω-3 polyunsaturated fatty acids (PUFAs) from postweaning until adulthood on T-lymphocyte proliferation, T-lymphocyte subpopulations (helper and cytotoxic), and production of cytotoxic mediators by macrophages in tumor-bearing rodents. Methods Weanling male Wistar rats received a normal low-fat (40 g/kg of diet) chow diet or a high-fat (300 g /kg) diet that included fish or sunflower oil or blends of fish and sunflower oils to yield ω-6:ω-3 PUFA ratios of approximately 6:1, 30:1, and 60:1 ad libitum. After 8 wk, 50% of rats in each group were inoculated with 1 mL of 2 × 107 Walker 256 cells. Fourteen days after tumor inoculation, animals were killed and lymphocytes and macrophages were obtained for study. Results The diets richest in ω-6 PUFA resulted in higher proliferation of thymus, spleen, and gut-associated lymphocytes compared with the chow diet irrespective of tumor burden. In contrast, the fish oil diet resulted in lower proliferation of thymus and spleen lymphocytes compared with the chow diet. Diets rich in ω-6 PUFA decreased the proportion of CD8+ lymphocytes. In non–tumor-bearing and tumor-bearing rats, hydrogen peroxide production by macrophages was highest in rats that consumed diets high in ω-3 PUFAs. Superoxide and nitric oxide production were little affected by the dietary ratio of ω-6 to ω-3 PUFAs. Conclusion Dietary ω-6 and ω-3 PUFA contents alter immune function in non–tumor-bearing and tumor-bearing rats. The ω-3 PUFAs decreased T-cell proliferation but increased hydrogen peroxide production compared with ω-6 PUFAs. Decreased tumor growth and cachexia and increased survival previously reported for fish oil in Walker 256 tumor-bearing rats may be related to improved macrophage function rather than to improved T-cell function.