Effects of dietary restriction or swimming on lymphocytes and macrophages functionality from old rats.

Although aging compromises the functionality of macrophages (MΦ) and lymphocytes (LY), and dietary restriction (DR) and exercise partially counterbalance immunosenescence, it is unknown what effects of both strategies have on the functionality of these immune cells. Rats were randomly distributed into adult control (AD), older group (OLD), older submitted to 50% of DR (DR) and older submitted to swimming (EX) (n = 10 in each group). The function of immune cells (proliferative index, phagocytic capacity and H2O2 production), the weight and protein content of lymphoid organs (thymus and spleen), plasma glutamine concentration, interleukins (IL-1, IL-2, IL-6) and, immunoglobulins (IgA and IgG) were analysed. There was an increase of 74% in body weight in aged animals as compared with the AD group, while body weight reduced 19% in the DR as compared with the OLD group. Swimming training stimulated MΦ phagocytosis, while the EX group presented a decrease of the proliferative capacity of LY from the mesenteric lymph nodes (44% and 62%, respectively), when stimulated with ConA and LPS as compared with the old rats. These data demonstrated that DR and exercise affects differentially MΦ and LY function.

Moderate exercise increases the metabolism and immune function of lymphocytes in rats.

Exercise modulates both glucose and glutamine metabolism which influences lymphocyte function. We investigated the influence of chronic moderate exercise on glucose and glutamine metabolism in lymphocytes, the associated influence on proliferation, and cytokine and immunoglobulin production. Male Wistar rats (8 weeks old) were placed in an exercise training group (N = 15, 1 h day(-1) at 60 % VO2max, 5 days week(-1)) for 8 weeks of exercise, or a sedentary control group. Twenty-four hours following the final training session, lymphocytes were separated, and the incorporation of [U-14C]-glucose, [U-14C]-glutamine, and [2-14C]-thymidine from the supernatant was measured. The activity of glucose-6-phosphate dehydrogenase, hexokinase, and glutaminase was measured. Lymphocytes were stimulated with ConA and LPS and incubated with the Mycobacterium bovis bacille Calmette-Guerin (BCG) vaccine and plasma IgG and IgE were measured. Glutamine metabolism increased in both T and B lymphocytes in the trained group. In the trained group, proliferative capacity increased T lymphocytes under ConA stimulation, and increased B lymphocytes with LPS. There was a significant increase in IL-2 production and decrease in IL-4 in the trained group compared with sedentary controls. IL-2R and TNFR increased in trained rats while IL-4R decreased and were more pronounced in T lymphocytes compared with B lymphocytes. In both lymphocyte subsets, exercise training significantly increased the expression of CD54+ and CD30+ cell markers. Exercise training increased plasma IgG compared with the sedentary group. In conclusion, moderate exercise training improves immune function and metabolism in T and B lymphocytes, reflecting an increased ability to respond to immune challenges.

Effect of exercise on glutamine metabolism in macrophages of trained rats.

This study investigated the effect of exercise on glutamine metabolism in macrophages of trained rats. Rats were divided into three groups: sedentary (SED); moderately trained (MOD) rats that were swim trained 1 h/day, 5 days/week for 6 weeks; and exhaustively trained (EXT) rats that were similarly trained as MOD for 5 weeks and, in the 6th week, trained in three 1-h sessions/day with 150 min of rest between sessions. The animals swam with a load equivalent to 5.5% of their body weight and were killed 1 h after the last exercise session. Cells were collected, and glutamine metabolism in macrophage and function were assayed. Exercise increased phagocytosis in MOD when compared to SED (34.48 +/- 1.79 vs 15.21 +/- 2.91%, P < 0.05); however, H(2)O(2) production was higher in MOD (75.40 +/- 3.48 nmol h x 10(5) cell(-1)) and EXT (79.20 +/- 1.18 nmol h x 10(5) cell(-1)) in relation to SED (32.60 +/- 2.51 nmol h x 10(5) cell(-1), P < 0.05). Glutamine consumption increased in MOD and EXT (26.53 +/- 3.62 and 19.82 +/- 2.62 nmol h x 10(5) cell(-1), respectively) relative to SED (6.72 +/- 0.57 nmol h x 10(5) cell(-1), P < 0.05). Aspartate increased in EXT (9.72 +/- 1.14 nmol h x 10(5) cell(-1)) as compared to SED (1.10 +/- 0.19 nmol h x 10(5) cell(-1), P < 0.05). Glutamine decarboxylation was increased in MOD (12.10 +/- 0.27 nmol h x 10(5) cell(-1)) and EXT (16.40 +/- 2.17 nmol h x 10(5) cell(-1)) relative to SED (1.10 +/- 0.06 nmol h x 10(5) cell(-1), P < 0.05). This study suggests an increase in macrophage function post-exercise, which was supported by enhanced glutamine consumption and metabolism, and highlights the importance for glutamine after exercise.

Effects of acute exhaustive physical exercise upon glutamine metabolism of lymphocytes from trained rats.

Transitory immunosupression is reported after intense exercise, especially after an increase in training overload and in overtraining. The influence of intense exercise on plasma hormones and glutamine concentration may contribute to this effect. However, the effect of such exercise-induced changes upon lymphocyte and glutamine metabolism is not known. We compared glutamine metabolism in lymphocytes in sedentary (SED) and trained rats. Rats from the moderate group (MOD) swam for 6 weeks, 1 h/day, in water at 32+/-1 degrees C, with a load of 5.5% body weight attached to the tail. Animals from the exhaustive group (EXT) trained like MOD, with training increasing to 3 times 1 h a day during the last week, with 150 min rest between each bout. Animals were killed immediately after the last training bout. We observed reduced concentrations of plasma glucose (p<0.05), glutamine (p<0.05), glutamate (p<0.05) in EXT compared to SED. In MOD, decreases in glutamine (p<0.05) were observed. Analyzing lymphocyte metabolism, we observed an increase in lactate production and glutamine consumption (p<0.05) in MOD (p<0.05) compared to SED and a decrease in glutamine consumption (p<0.05) and aspartate production in EXT. An increase in the proliferative response of lymphocytes in MOD and EXT was also observed when stimulated by ConA and LPS similarly to SED. Acute exercise promoted decreased glutamine plasma concentration and changes in glutamine metabolism that did not impair lymphocyte proliferation in exhaustive trained rats.

Beta-hydoxy-beta-methylbutyrate supplementation affects Walker 256 tumor-bearing rats in a time-dependent manner.

BACKGROUND & AIMS: Cancer cachexia affects intermediary metabolism with intense and general catabolism. Walker 256 tumor is a model injected either subcutaneously (Sc) or intraperitoneally (Ip), with different metabolic features. Beta-hydroxy beta-methylbutyrate (HMbeta) is a leucine metabolite with anti-catabolic properties, the aim of this study being to investigate its effects on metabolic parameters in both tumor models. METHODS: Controls (subcutaneous control group (ScC) and intraperitoneal control group (IpC)) and supplemented animals (subcutaneous supplemented group (ScS) and intraperitoneal supplemented group (IpS)) showed these results. RESULTS: Protein Sc values were (47.8%) lower than Ip groups. Sc group fat content was (65.16%) higher than Ip groups. Liver glycogen value for Sc groups was (38.4%) higher than Ip groups. Muscle glycogen value for Sc groups were (2.75 times) higher than Ip groups. Corticosterone and insulin values were lower (44.53%) and higher (45.94%), respectively, in Sc when compared with Ip groups. Glucose and lactate values for ScS were the lowest (61.7% and 41.53%) compared to other groups. ScC glutamine value was the highest (40.8%) of all groups. Glutamate Sc values were (42.65%) lower than Ip groups. Sc groups showed greater survival time compared with Ip groups. ScS group showed 100% increase in survival time when compared with ScC. CONCLUSIONS: HMbeta supplementation can increase survival time and promotes metabolic changes in cancer-bearing animals, but it seems to work in a time-dependent manner.

Reduced maximal oxygen consumption and overproduction of proinflammatory cytokines in athletes.

OBJECTIVE: It was the aim of this study to evaluate whether chronic pain in athletes is related to performance, measured by the maximum oxygen consumption and production of hormones and cytokines. METHODS: Fifty-five athletes with a mean age of 31.9 +/- 4.2 years engaged in regular competition and showing no symptoms of acute inflammation, particularly fever, were studied. They were divided into 2 subgroups according to the occurrence of pain. Plasma concentrations of adrenaline, noradrenaline, cortisol, prolactin, growth hormone and dopamine were measured by radioimmunoassay, and the production of the cytokines interleukin (IL)-1, IL-2, IL-4, IL-6, tumor necrosis factor-alpha, interferon-alpha and prostaglandin E(2) by whole-blood culture. Maximal oxygen consumption was determined during an incremental treadmill test. RESULTS: There was no change in the concentration of stress hormones, but the athletes with chronic pain showed a reduction in maximum oxygen consumption (22%) and total consumption at the anaerobic threshold (25%), as well as increased cytokine production. Increases of 2.7-, 8.1-, 1.7- and 3.7-fold were observed for IL-1, IL-2, tumor necrosis factor-alpha and interferon-alpha, respectively. CONCLUSIONS: Our data show that athletes with chronic pain have enhanced production of proinflammatory cytokines and lipid mediators and reduced performance in the ergospirometric test.

The profile of melatonin production in tumour-bearing rats.

The pineal gland is involved in the regulation of tumour growth through the anticancer activity of melatonin, which presents immunomodulatory, anti-proliferative and anti-oxidant effects. In this study we measured melatonin content directly in the pineal gland, in an attempt to clarify the modulation of pineal melatonin secretory activity during tumour growth. Different groups of Walker 256 carcinosarcoma bearing rats were sacrificed at 12 different time points during 24h (12h:12h light/dark cycle) on different days during the tumour development (on the first, seventh and fourteenth day after tumour inoculation). Melatonin content in the pineal gland was determined by high-performance liquid chromatography with electrochemical detection. During tumour development the amount of melatonin secreted increased from 310.9 ng/mg of protein per day from control animals, to 918.1 ng/mg of protein per day 14 days after tumour implantation, and there were changes in the pineal production profile of melatonin. Cultured pineal glands obtained from tumour-bearing rats turned out to be less responsive to noradrenaline, suggesting the existence, in vivo, of putative factor(s) modulating pineal melatonin production. The results demonstrated that during tumour development there is a modification of pineal melatonin production daily profile, possibly contributing to cachexia, associated to changes in pineal gland response to noradrenaline stimulation.

Alteracão da relacão testosterona: cortisol induzida pelo treinamento de forca em mulheres / Alteration of testosterone: cortisol ratio induced by resistance training in women

A razão entre a concentracão de testosterona e cortisol (T:C) é freqüentemente utilizada como indicativo do nível de estresse imposto pelo exercício. Alteracões na concentracão destes hormônios são responsáveis por modular diversas respostas induzidas pelo treinamento, como hipertrofia e ganho de forca. O objetivo do presente estudo foi examinar a influência do protocolo de treinamento de forca, conhecido como múltiplas-séries (MS), sobre o ganho de forca, de resistência muscular localizada e a relacão entre a concentracão de hormônios catabólicos (cortisol) e anabólicos (testosterona). Para testar esta hipótese cinco jovens do sexo feminino com um ano de experiência em treinamento de forca foram submetidas ao protocolo MS. As amostras de sangue foram coletadas antes e imediatamente após o exercício, no primeiro dia e após oito semanas de treinamento. Os testes de 1-RM e de repeticões máximas foram realizados também no início e ao final das oito semanas de treinamento de forca. Não foram observadas alteracões na massa corporal, no IMC, na percentagem de massa gorda e na forca máxima (1-RM) no supino, no agachamento e na rosca direta. O número de repeticões máximas a 50 por cento de 1-RM foi aumentado apenas para o supino (p < 0,05). Não foi observada alteracão na concentracão de testosterona total. Com relacão à concentracão plasmática de cortisol, após oito semanas de treino, na situacão de repouso, foi reduzida (38 por cento - p < 0,05). Em conseqüência da atenuacão da secrecão de cortisol após oito semanas de treinamento, a razão T:C apresentou elevacão de 20 por cento na situacão de repouso (p < 0,05). Apesar de não terem sido detectadas alteracões funcionais nos testes de 1-RM e repeticões máximas, o método MS induziu um quadro hormonal favorável ao anabolismo protéico.