Exercise prevents the effects of experimental arthritis on the metabolism and function of immune cells.

Active lymphocytes (LY) and macrophages (MPhi) are involved in the pathophysiology of rheumatoid arthritis (RA). Due to its anti-inflammatory effect, physical exercise may be beneficial in RA by acting on the immune system (IS). Thus, female Wistar rats with type II collagen-induced arthritis (CIA) were submitted to swimming training (6 weeks, 5 days/week, 60 min/day) and some biochemical and immune parameters, such as the metabolism of glucose and glutamine and function of LY and MPhi, were evaluated. In addition, plasma levels of some hormones and of interleukin-2 (IL-2) were also determined. Results demonstrate that CIA increased lymphocyte proliferation (1.9- and 1.7-fold, respectively, in response to concanavalin A (ConA) and lipopolysaccharide (LPS)), as well as macrophage H(2)O(2) production (1.6-fold), in comparison to control. Exercise training prevented the activation of immune cells, induced by CIA, and established a pattern of substrate utilization similar to that described as normal for these cells. Exercise also promoted an elevation of plasma levels of corticosterone (22.2%), progesterone (1.7-fold) and IL-2 (2.6-fold). Our data suggest that chronic exercise is able to counterbalance the effects of CIA on cells of the IS, reinforcing the proposal that the benefits of exercise may not be restricted to aerobic capacity and/or strength improvement.

Changes in glucose and glutamine lymphocyte metabolisms induced by type I interferon α.

In lymphocytes (LY), the well-documented antiproliferative effects of IFN-α are associated with inhibition of protein synthesis, decreased amino acid incorporation, and cell cycle arrest. However, the effects of this cytokine on the metabolism of glucose and glutamine in these cells have not been well investigated. Thus, mesenteric and spleen LY of male Wistar rats were cultured in the presence or absence of IFN-α, and the changes on glucose and glutamine metabolisms were investigated. The reduced proliferation of mesenteric LY was accompanied by a reduction in glucose total consumption (35%), aerobic glucose metabolism (55%), maximal activity of glucose-6-phosphate dehydrogenase (49%), citrate synthase activity (34%), total glutamine consumption (30%), aerobic glutamine consumption (20.3%) and glutaminase activity (56%). In LY isolated from spleen, IFNα also reduced the proliferation and impaired metabolism. These data demonstrate that in LY, the antiproliferative effects of IFNα are associated with a reduction in glucose and glutamine metabolisms.

Exercise as a Time-conditioning Effector in Chronic Disease: a Complementary Treatment Strategy.

Exercise has been widely believed to be a preventive and therapeutic aid in the treatment of various pathophysiological conditions such as cardiovascular disease and cancer. A common problem associated with such pathologies is cachexia, characterized by progressive weight loss and depletion of lean and fat body mass, and is linked to poor prognosis. As this syndrome comprises changes in many physiological systems, it is tempting to assume that the modulation of the psychoneuroimmunoendocrine axis could attenuate or even prevent cachexia progression in cancer patients. Cancer cachexia is characterized by a disruption in the rhythmic secretion of melatonin, an important time-conditioning effector. This hormone, secreted by the pineal gland, transmits circadian and seasonal information to all organs and cells of the body, synchronizing the organism with the photoperiod. Considering that exercise modulates the immune response through at least two different mechanisms-metabolic and neuroendocrine-we propose that the adoption of a regular exercise program as a complementary strategy in the treatment of cancer patients, with the exercise bouts regularly performed at the same time of the day, will ameliorate cachexia symptoms and increase survival and quality of life.

Does exercise training interfere with the effects of L-carnitine supplementation?

OBJECTIVE: We investigated the effect of L-carnitine supplementation on carnitine content in muscle fiber, glucose, and fatty acid metabolism and on performance in trained rats. METHODS: Male Wistar rats received a daily dose of 28 mg/kg, intragastrically, during the last 4 wk of a 6-wk moderate-intensity training program. The contents of carnitine and coenzyme A were evaluated in muscle fiber and its capacity to metabolize labeled glucose, oleate, and pyruvate. The ergogenic effect of the amine was assessed by the evaluation of time until exhaustion in an exercise session. The results were analyzed by analysis of variance and Tukey's post hoc test, and significance was set at P < 0.05. RESULTS: In our model, carnitine supplementation increased time until exhaustion (14.0%), similar to that observed for trained rats, but the effect was even greater (30.3% increase) in the supplemented and trained rats. Carnitine supplementation increased oleate decarboxylation (17% for sedentary rats and 119% for trained rats) and decreased glucose (29.7% and 45% for sedentary and trained rats, respectively) and [2-(14)C ]-pyruvate (45.9% and 61% for sedentary and trained rats, respectively) decarboxylation. The flux of [1-(14)C]-pyruvate through the Krebs cycle increased by 32% and 70% for supplemented sedentary and trained rats, respectively. The training protocol also increased [1-(14)C]-pyruvate decarboxylation by 32%. The cytosolic content of free, long-chain, and short-chain acyl-carnitine increased in the soleus muscle obtained from supplemented sedentary rats by 28%, 117%, and 16%, respectively, and 99%, 205%, and 32% for the muscle from supplemented trained rats. CONCLUSIONS: This study showed that carnitine supplementation increases fatty acid oxidation in skeletal muscle by a mechanism that includes increasing total carnitine content in soleus muscle mitochondria and the total content of acyl-carnitine. The most interesting finding was that the effect of supplementation was even greater in trained rats that had received 3-wk supplementation of carnitine.

Branched-chain amino acid supplementation and the immune response of long-distance athletes.

OBJECTIVE: Intense long-duration exercise has been associated with immunosuppression, which affects natural killer cells, lymphokine-activated killer cells, and lymphocytes. The mechanisms involved, however, are not fully determined and seem to be multifactorial, including endocrine changes and alteration of plasma glutamine concentration. Therefore, we evaluated the effect of branched-chain amino acid supplementation on the immune response of triathletes and long-distance runners. METHODS: Peripheral blood was collected prior to and immediately after an Olympic Triathlon or a 30k run. Lymphocyte proliferation, cytokine production by cultured cells, and plasma glutamine were measured. RESULTS: After the exercise bout, athletes from the placebo group presented a decreased plasma glutamine concentration that was abolished by branched-chain amino acid supplementation and an increased proliferative response in their peripheral blood mononuclear cells. Those cells also produced, after exercise, less tumor necrosis factor, interleukins-1 and -4, and interferon and 48% more interleukin-2. Supplementation stimulated the production of interleukin-2 and interferon after exercise and a more pronounced decrease in the production of interleukin-4, indicating a diversion toward a Th1 type immune response. CONCLUSIONS: Our results indicate that branched-chain amino acid (BCAA) supplementation recovers the ability of peripheral blood mononuclear cells proliferate in response to mitogens after a long distance intense exercise, as well as plasma glutamine concentration. The amino acids also modify the pattern of cytokine production leading to a diversion of the immune response toward a Th1 type of immune response.