Long-term exercise training selectively alters serum cytokines involved in fever.

Long-term exercise training selectively alters serum cytokines involved in fever. Chronic exercise training has a number of effects on the immune system that may mimic the physiological response to fever. Female rats that voluntarily exercise on running wheels develop an elevated daytime core temperature after several weeks of training. It remains to be seen whether the elevation in daytime temperature involves inflammatory patterns characteristic of an infectious fever. We assessed whether chronic exercise training in the rat would alter levels of cytokines involved in fever. Female Sprague Dawley rats at 45 days of age weighing 90-110 g were divided into two groups (exercise and sedentary) and housed at an ambient temperature of 22( degrees )C. Interleukin-1 beta (IL-1beta), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-alpha), iron, and zinc levels were analyzed. Rats underwent 8 weeks of exercise on running wheels. Exercise led to altered levels of some key cytokines that are involved in fever. Exercise animals had significantly higher IL-1beta levels and lower IL-10 levels compared to sedentary animals. Although IL-6 levels were slightly lower in the exercise animals, these levels were not significantly affected by training. TNF-alpha activity was similar in the two groups. Training also led to a slight increase in serum zinc and decrease in serum unsaturated iron binding capacity (UIBC). The data suggest that chronic exercise training evokes immune responses that mimic some, but not all, aspects of fever. This may explain why exercise leads to elevated daytime core temperature.

Effects of chronic exercise conditioning on thermal responses to lipopolysaccharide and turpentine abscess in female rats.

Chronic exercise conditioning has been shown to alter basal thermoregulatory processes as well as the response to inflammatory agents. Two such agents, lipopolysaccharide (LPS) and turpentine (TPT) are inducers of fever in rats. LPS, given intraperitoneally (i.p.), involves a systemic inflammatory response whereas TPT given intramuscularly (i.m.) elicits a localized inflammation. We assessed if chronic exercise training in the rat would alter the thermoregulatory response to LPS and TPT. Core temperature (T (c)) and motor activity were monitored by radiotelemetry. Female Sprague Dawley rats were divided into two groups (trained and sedentary) and housed at an ambient temperature of 22 degrees C. Animals voluntarily trained on running wheels for 8 weeks. In the first study, trained and sedentary female rats were injected i.p. with LPS (50 microg/kg) or an equal volume of 0.9% normal saline. In another study, trained and sedentary female rats were injected i.m. with TPT (10 microl)/rat or an equal volume of 0.9% normal saline. The time course of the LPS fever was very short compared to TPT. TPT injected animals displayed a smaller but more prolonged fever compared to LPS; however, training accentuated the febrile response to LPS (DeltaT (c)=0.6 degrees C in sedentary and 1.2 degrees C in trained). Training had a slight suppression on TPT-induced fever during the daytime but had no effect on motor activity or nighttime T (c). In contrast, exercise training led to a marked increase in the pyrogenic effects of LPS. We conclude that the effect of exercise training and source of infection (i.e., systemic versus localized in muscle) on fever is directly linked to type of pyrogenic agent.

Effects of exercise conditioning on thermoregulatory responses to repeated administration of chlorpyrifos.

Little is known about the effects of physical activity (i.e., exercise training) on susceptibility to environmental toxicants. Chlorpyrifos (CHP), an organophosphate (OP) insecticide, affects thermoregulation, causing an acute period of hypothermia followed by a delayed fever. Since exercise conditioning alters the thermoregulatory responses of rodents, this study examined whether exercise training would alter the thermoregulatory response to repeated CHP administration in the female Sprague-Dawley rat. Core temperature (T(c)) and motor activity (MA) were monitored by radiotelemetry in rats housed at an ambient temperature (T(a)) of 22 degrees C. The rats either were provided with continuous access to running wheels (exercise group) or were housed in standard cages without wheels (sedentary group). The exercise group rats ran predominantly at night with an average of 7.6 km/24h. After 8 weeks the rats in both groups were gavaged daily with corn oil or 10mg/kg CHP (dissolved in corn oil) for 4 days. CHP induced an immediate hypothermic response followed by a delayed fever throughout the next day in the sedentary group rats after the first three doses of CHP. The exercise group rats showed no hypothermia after the first dose of CHP. However, they became hypothermic after the second and third doses of CHP. The exercise group rats developed a smaller daytime fever after each dose of CHP compared to the sedentary group rats. Overall, exercise training attenuated the hypothermic and febrile effects of repeated CHP. Thus, the data suggest that a sedentary lifestyle may increase the sensitivity to OP insecticides. Exercise training was also associated with a more rapid recovery of plasma cholinesterase activity.

The effect of a genetic variant for obesity and Type 2 Diabetes on the therapeutic potential of exercise and calorie restrictive diets in Zucker rats.

Obesity and Type 2 Diabetes are modern pandemics caused by unique genetic-environmental interactions and distinguished by almost universal treatment failures. Relative influences of genome and lifestyle changes on an adult onset Obesity-Type 2 diabetes phenotype were explored. Zucker rats, a recessive model of genetic obesity-Type 2 Diabetes (117 fa/fa and 98 Fa/fa) were used. Dietary induced obesity (DIO) was imposed via a high fat diet on one-half; and one-half were forced to swim daily (EX). After 6 weeks, 78 animals were placed on a calorie (Kcal) restrictive diet for 6 more weeks. Genotype accounted for > 20% additional insulin resistance and obesity and modulated the effects of DIO and EX in adult animals exhibiting obesity-Type 2 diabetes. Only DIO gains were responsive to Kcal restriction. EX effects on insulin resistance were mediated by both Kcal restriction and genotype. Kcal restriction directly reduced hyperglycemia. Genetic variation was the major determinant of obesity and Type 2 Diabetes in Zucker rats. Genetically induced obesity and insulin sensitivity were resistant to EX and Kcal restriction; DIO and hyperglycemia were responsive to both. Successful treatment of Type 2 Diabetes requires understanding of how genotype may continue to modify adult responses to lifestyle change.

The effect of opioid antagonism on food intake behavior and body weight in a biobehavioral model of obese binge eating.

The obese Zucker rat (OZR) exhibits a hyperphagic eating pattern similar to the obese binge eater. Dynorphin, an endogenous agonist of the kappa receptor, is associated with regulation offood intake. Lessened sensitivity to opioid antagonists and/or increased central dynorphin levels may contribute to the hyperphagic eating pattern observed in the OZR. This study examined the temporal effect of a single intracerebroventricular (ICV) dose of nor-binaltorphimine (NBNI), a specific and long-lasting kappa opioid antagonist, on food intake, body weight, and satiety measures (meal size and the shape of the cumulative food intake curve [CFIC]) in adult male OZRs. Analysis of individual subjects revealed a differential response to opioid antagonism with respect to weight loss, reduction in food intake, and change in the slope of the CFIC, with some responding and others responding poorly. Repeated-measures analysis of variance showed a significant decrease in body weight (P = 0.001) and food intake (P = 0.03) in responders compared to poor responders and controls. Satiation was influenced to a greater extent in responders, who showed a significant reduction in meal size and a greater change in the CFICfor the largest meal of the day toward a pattern of satiation. These data suggest that a differential response to chronic opioid antagonism may exist in the OZR.

Trajectories of cognitive recovery following a minor brain injury.

Minor brain injury (MBI) is the most frequently diagnosed head trauma in the United States, with treatment costing more than $1.5 billion annually and many patients incapacitated for months following injury. The purpose of this study was to characterize the brain function disruptions associated with MBI and to determine the time trajectory of recovery, using a theoretical model of attention. Distractibility, impulsivity, irritability, and impaired executive functioning were demonstrated in all participants during the 24 hr after injury. Twenty percent of participants continued to complain of distractibility, impulsivity, and/or irritability throughout the 30-day study. Loss of consciousness was shown to confound participants' healing trajectories. These results suggest that standard emergency room treatment following MBI is inadequate and should include discharge directives to reduce cognitive demands for at least 48 hr at a minimum, for 30 days or longer for those with loss of consciousness.