Showing papers in "Exercise Immunology Review in 2006"

Interleukin-6 in acute exercise and training: what is the biological relevance?

Abstract: It is now recognized that contracting skeletal muscle may synthesize and release interleukin-6 (IL-6) into the interstitium as well as into the systemic circulation in response to a bout of exercise. Although several sources of IL-6 have been demonstrated, contracting muscles contributes to most of the IL-6 present in the circulation in response to exercise. The magnitude of the exercise-induced IL-6 response is dependent on intensity and especially duration of the exercise, while the mode of exercise has little effect. Several mechanisms may link muscle contractions to IL-6 synthesis: Changes in calcium homeostasis, impaired glucose availability, and increased formation of reactive oxygen species (ROS) are all capable of activating transcription factors known to regulate IL-6 synthesis. Via its effects on liver, adipose tissue, hypothalamic-pituitary-adrenal (HPA) axis and leukocytes, IL-6 may modulate the immunological and metabolic response to exercise. However, prolonged exercise involving a significant muscle mass in the contractile activity is necessary in order to produce a marked systemic IL-6 response. Furthermore, exercise training may reduce basal IL-6 production as well as the magnitude of the acute exercise IL-6 response by counteracting several potential stimuli of IL-6. Accordingly, a decreased plasma IL-6 concentration at rest as well as in response to exercise appears to characterize normal training adaptation.

Exercise and Toll-like receptors.

Abstract: Toll-like receptors (TLRs) are highly conserved trans-membrane proteins that play an important role in the detection and recognition of microbial pathogens The key product of TLR signalling in antigen presenting cells is the production of inflammatory cytokines and proteins The TLR pathway plays an important role in mediating whole body inflammation, which has been implicated in the development of chronic disease An accumulation of chronic, low-grade inflammation is common in individuals that live a sedentary lifestyle; however, the mechanism underlying this connection is not fully understood There is evidence to show that TLRs may be involved in the link between a sedentary lifestyle, inflammation, and disease Recent studies have shown that both acute aerobic and chronic resistance exercise resulted in decreased monocyte cell-surface expression of TLRs Furthermore, a period of chronic exercise training decreases both inflammatory cytokine production and the cell-surface expression of TLR4 on monocytes These effects may contribute to post-exercise immunodepression and the reported higher susceptibility to infection in athletes However over the long-term, a decrease in TLR expression may represent a beneficial effect because it decreases the inflammatory capacity of leukocytes, thus altering whole body chronic inflammation The precise physiological stimulus mediating an exercise-induced decrease in cell-surface TLR expression is not known; however a number of possible signals have been implicated including anti-inflammatory cytokines, stress hormones and heat shock proteins

Systemic inflammatory responses to maximal versus submaximal lengthening contractions of the elbow flexors.

Abstract: We compared changes in markers of muscle damage and systemic inflammation after submaximal and maximal lengthening muscle contractions of the elbow flexors. Using a cross-over design, 10 healthy young men not involved in resistance training completed a submaximal trial (10 sets of 60 lengthening contractions at 10% maximum isometric strength, 1 min rest between sets), followed by a maximal trial (10 sets of three lengthening contractions at 100% maximum isometric strength, 3 min rest between sets). Lengthening contractions were performed on an isokinetic dynamometer. Opposite arms were used for the submaximal and maximal trials, and the trials were separated by a minimum of two weeks. Blood was sampled before, immediately after, 1 h, 3 h, and 1-4 d after each trial. Total leukocyte and neutrophil numbers, and the serum concentration of soluble tumor necrosis factor-alpha receptor 1 were elevated after both trials (P < 0.01), but there were no differences between the trials. Serum IL-6 concentration was elevated 3 h after the submaximal contractions (P < 0.01). The concentrations of serum tumor necrosis factor-alpha, IL-1 receptor antagonist, IL-10, granulocyte-colony stimulating factor and plasma C-reactive protein remained unchanged following both trials. Maximum isometric strength and range of motion decreased significantly (P < 0.001) after both trials, and were lower from 1-4 days after the maximal contractions compared to the submaximal contractions. Plasma myoglobin concentration and creatine kinase activity, muscle soreness and upper arm circumference all increased after both trials (P < 0.01), but were not significantly different between the trials. Therefore, there were no differences in markers of systemic inflammation, despite evidence of greater muscle damage following maximal versus submaximal lengthening contractions of the elbow flexors.

Moderate exercise early after influenza virus infection reduces the Th1 inflammatory response in lungs of mice

Abstract: We have previously shown that moderate exercise significantly increased survival after influenza virus (A/PR/8/34) infection in mice. We hypothesized that this brief duration of exercise would either increase innate immune defences and/or shift the immune response from a Th1 inflammatory to a Th2 anti-inflammatory response resulting in decreased lung pathology. Adult male BALB/cByJ mice (5-6 months old) were infected with 50 microL of A/PR/8/34 virus (40HAU) intranasally and randomized to either an exercise (EX) or sedentary (SED) group. EX mice performed 20-30 min of moderate exercise (8-12 m/min) on a motorized treadmill 4 hr post-infection and then exercised similarly for 4 consecutive days. SED mice were exposed to similar environmental conditions but did not exercise. Mice from both EX and SED groups were sacrificed 1, 3, or 5 days post-infection (p.i.) and lungs, mediastinal lymph nodes (MLNs) and spleens were harvested. EX significantly reduced total cellular infiltration and IFN-gamma gene expression in lungs at Days 3 and 5 p.i. and there was a qualitative shift in the expression of cytokines in the lung from a Th1 to a Th2 response. There was also a tendency toward a reduction in influenza M1 protein mRNA expression. There was no difference in IFN-beta protein levels between groups. These data suggest that moderate exercise when applied early after infection shifts the immune response away from a Th1 profile in mice infected with influenza virus. This exercise-induced shift in immune response may be responsible for improved survival after influenza virus infection.

The implication of alterations in leukocyte subset counts on immune function.

Abstract: Changes elicited by physical exercise in the numbers or the activity of blood T lymphocytes, NK cells and neutrophils are sometimes considered as indicators of altered immunocompetence. By comparing the pathological conditions, in which the changes in the numbers of cells resemble observations in the exercise studies, however we notice large discrepancies in the clinical manifestations. Supplementary information regarding the differences in cytokines and mediators responsible for altered distributions helps to explain this difference and the significance of altered distribution of the cells for immunocompetence. Alterations in the numbers and activities of T lymphocytes, NK cells and neutrophils may serve as markers of sympathetic and glucocorticoid activities, which per se may influence immunocompetence not necessarily deterioration.

Regulation of immediate early gene expression by exercise: short cuts for the adaptation of immune function.

Abstract: Onset of physical activity induces a wide variety of rapid biophysical and biochemical responses that act on cells and lead to a wide range of phenotypic adaptations. Here we elucidate the role of immediate early gene (IEG) expression as a first line of transcriptional response that mediates protein neosynthesis and leads to adaptation of immune function. New posttranscriptional mechanisms have been described that speed up transcriptional responses. These include RNA-RNA interactions such as those exploited by miRNAs and stimulus-dependent cytoplasmic polyadenylation. We describe these shortcuts that modulate expression and discuss the challenges of accurately measuring them using various transcriptomic screening and quantification approaches. Although there is high complexity of the upstream as well as the downstream pathways that lead to IEG expression, IEG expression itself may only show a limited number of response patterns. Focusing transcriptomic approaches in exercise immunology at the IEG-level may facilitate the discovery of exercise-specific transcriptional signatures.

Physiological improvements and health benefits during an exercise-based comprehensive rehabilitation program in medically complex patients.

Abstract: OBJECTIVES To determine the effects of an exercise-based comprehensive rehabilitation program on the physiological, health, and cost benefit in medically complex patients. DESIGN Case series SETTING Comprehensive rehabilitation centers. PARTICIPANTS Elderly chronically ill men (n = 39, age = 75.3 +/- 1.4) and women (n = 74, age = 76.5 +/- 0.9 years). INTERVENTION Patients participated in individualized physical therapy with therapeutic exercises (stretching, strengthening, endurance, balance, sitting and standing dynamic exercises) three times/week for three months under the supervision of a physician. MEASUREMENTS Upper (back) and lower (leg flexors) extremity strength, aerobic power as measured by metabolic equivalents (METS) at 80% of age predicted maximal heart rate (APMHR), physical functioning and mental health as assessed by the Short Form-36 (SF-36) questionnaire, and medical events (falls, physician visits, and hospitalizations) questionnaire was collected at baseline and after three months of the program. RESULTS Strength measures improved by approximately 30% (P < 0.05) as well as aerobic power improved by approximately 25% (P < 0.05) over the three-month period. There were significant improvements in two of the SF-36 Physical Component Scales: Physical Functioning (P < 0.05) and Role Physical (P < 0.05); plus, there were significant improvements in all four of the Mental Component Scales: Vitality (P < 0.05), Social Functioning (P < 0.05), Role Emotional (P < 0.05), and Mental Health (P < 0.05). There were significant reductions in fall rate (P < 0.05), physician visits (P < 0.05), and hospitalizations (P < 0.05). CONCLUSION Patients improve physical capacity, which result in improvements in health status with concurrent reductions in healthcare utilization during a comprehensive rehabilitation program.