White adipose tissue IFN-γ expression and signalling along the progression of rodent cancer cachexia.

Cachexia is associated with increased morbidity and mortality in cancer. The White adipose tissue (WAT) synthesizes and releases several pro-inflammatory cytokines that play a role in cancer cachexia-related systemic inflammation. IFN-γ is a pleiotropic cytokine that regulates several immune and metabolic functions. To assess whether IFN-γ signalling in different WAT pads is modified along cancer-cachexia progression, we evaluated IFN-γ receptors expression (IFNGR1 and IFNGR2) and IFN-γ protein expression in a rodent model of cachexia (7, 10, and 14days after tumour implantation). IFN-γ protein expression was heterogeneously modulated in WAT, with increases in the mesenteric pad and decreased levels in the retroperitoneal depot along cachexia progression. Ifngr1 was up-regulated 7days after tumour cell injection in mesenteric and epididymal WAT, but the retroperitoneal depot showed reduced Ifngr1 gene expression. Ifngr2 gene expression was increased 7 and 14days after tumour inoculation in mesenteric WAT. The results provide evidence that changes in IFN-γ expression and signalling may be perceived at stages preceding refractory cachexia, and therefore, might be employed as a means to assess the early stage of the syndrome.

Short-term l-arginine supplementation attenuates elevation of interleukin 6 level after resistance exercise in overweight men.

BACKGROUND AND AIM: l-Arginine (l-arg) supplementation and resistance exercise can induce changes in inflammatory and anti-inflammatory cytokines; however, it has not been investigated in obese hypertensive men. This study examines the effects of short-term l-arg supplementation and acute resistance exercise (AREX) on cytokine levels in obese hypertensive men. METHODS: Eight obese hypertensive men aged 46 ± 6 yrs. with an average body weight of 92.56 ± 9.9 kg and a BMI of 31.68 ± 2.18 kg/m2 participated in a randomized, double-blinded, crossover study. The patients were distributed into exercise groups based on the type of supplementation (6 g/day of placebo or l-arg for 7 days). Supplementation periods were separated by a seven-day washout period. The AREX regimen consisted of eight exercises with an exercise intensity of 60% of 1 repetition maximum. The interleukins IL-1ra, IL-6, and IL-10 and the IL-6/IL10 ratio were determined at rest, immediately after exercise and 1 h after exercise sessions. RESULTS: IL-1ra levels exhibited a significant difference both immediately and 1 h after exercise when the l-arg and placebo groups were compared (P < 0.05). IL-6 levels increased significantly after exercise in the placebo group compared with the l-arg group (P < 0.05). The placebo group showed a decrease in the IL-10 levels 1 h after exercise compared with resting levels (P < 0.05). The IL-6/IL-10 ratio showed a statistically significant increase in the placebo group after exercise compared to the l-arg group (P < 0.05). CONCLUSIONS: LARG supplementation attenuates the cytokine increase after AREX, in particular peak IL-6 levels decrease and exercise induced decreases in IL-10 levels are attenuated.