P053 Effects of leucine-rich diet and exercise on inflammatory response produced by the tumour growth in rats

Abstract

Introduction The intense mobilisation of substrates during cancer induces a severe involuntary weight loss, leading to cachexia. Cytokines are important in the alteration of carbohydrate, lipid, and protein metabolism in cancer-cachexia. Methods We examined the effect of leucine-rich diet and exercise on the inflammatory response in Walker 256 tumour-bearing rats. Wistar rats submitted to aerobic exercise, and leucine-rich diet were distributed into 8 groups: C – control rats; TC – trained, W – tumour-bearing; TW – trained tumour-bearing, L – rats fed leucine diet, TL – trained rats fed leucine diet; LW – tumour-bearing fed leucine diet; TLW – trained tumour-bearing fed leucine diet. Results After 21 days, the tumour development induced a significant increase in the proinflammatory cytokines. Tumour necrosis factor (TNF-α) enhanced in tumour groups (W (2.57 ± 0.28), TW (3.2 ± 0.58), LW (2.67 ± 0.29), TLW (2.91 ± 0.75) compared to control groups C (1.60 ± 0.22), TC (1.84 ± 0.11), L (1.65 ± 0.18), TL (1.39 ± 0.15 pg/mL)). Interferon-γ (INF-γ) also increased significantly in tumour groups (W (172.3 ± 28.9), TW (153.0 ± 33.1), LW (238.8 ± 79.4), TLW (226.4 ± 82.1) vs control groups (C (88.3 ± 20.9), TC (68.4 ± 18.9), L (98.9 ± 43.5), TL (107.8 ± 50.6)). The serum concentration of interleukin-6 (IL-6) raised significantly in group W (408.5 ± 275.5) vs groups C (16.23 ± 4.8), TC (16.75 ± 1.35), TW (63.6 ± 10.4), L (27.6 ± 8.0), LW (31.9 ± 9.1) and TWL (43.8 ± 21.9). The trained-rats and leucine-fed group (TL) showed an increase in IL-6 vs control group C, but not as higher as verified in W group. The concentration of interleukin-1α (IL-1α) also increased in group W (40.64 ± 12.5), TL (53.5 ± 4.0), LW (39.9 ± 12.3) and TWL (43.4 ± 23.1) vs groups C (15.8 ± 3.5), TC (14.0 ± 2.3), TW (27.2 ± 11.7), L (20.3 ± 9.9). The interleukin 4 (IL-4), cytokine related to host defence response showed an increase in group TW (13.0 ± 10.4) vs groups C (3.7 ± 0.9), TC (5.3 ± 1.3), W (4.4 ± 0.9), L (5.3 ± 2.1), TL (7.2 ± 3.9), WL (8.5 ± 4.2) and TWL (3.9 ± 1.1). The anti-inflammatory cytokine, IL-10, increased in all groups with tumour, mainly in W group (2481 ± 736,4) compared to other groups (C (124,1 ± 33,06), TC (127,5 ± 40,0), L (75,66 ± 6,12), TL (87,21 ± 9,3)). The IL-10/TNF-apha ratio a marker of the intensity of the inflammatory condition was significant increased in all tumour-bearing groups vs control groups. Despite the accelerated tumour growth, exercise reduced tumour growth, as tumour mass and tumour/body weight ratio were lower than in the other groups. The tumour weight in the TWL group was around 57% less than in the W group. The WL and TW groups had tumour weight reduced in 24% and 28% less compared to W group, respectively. Conclusion Although the tumour development induced chronic inflammation in the production of proinflammatory cytokines in the development of cachexia, the effects produced by the association between exercise and leucine-rich diet showed benefit effects, probably improving the host responses. Supported by: Fapesp #2010/11328-9; #2009/11993-5.