Exercise Immunology Review最新文献

The purpose of this study was to examine sex differences in immune variables and upper respiratory tract infection (URTI) incidence in 18-35 year-old athletes engaged in endurance-based physical activity during the winter months. Eighty physically active individuals (46 males, 34 females) provided resting venous blood samples for determination of differential leukocyte counts, lymphocyte subsets and whole blood culture multi-antigen stimulated cytokine production. Timed collections of unstimulated saliva were also made for determination of saliva flow rate, immunoglobulin A (IgA) concentration and IgA secretion rate. Weekly training and illness logs were kept for the following 4 months. Training loads averaged 10 h/week of moderate-vigorous physical activity and were not different for males and females. Saliva flow rates, IgA concentration and IgA secretion rates were significantly higher in males than females (all P < 0.01). Plasma IgA, IgG and IgM concentrations and total blood leukocyte, neutrophil, monocyte and lymphocyte counts were not different between the sexes but males had higher numbers of B cells (P < 0.05) and NK cells (P < 0.001). The production of interleukins 1 beta, 2, 4, 6, 8 and 10, interferon-gamma and tumour necrosis factor-alpha in response to multi-antigen challenge were not significantly different in males and females (all P > 0.05). The average number of weeks with URTI symptoms was 1.7 +/- 2.1 (mean +/- SD) in males and 2.3 +/- 2.5 in females (P = 0.311). It is concluded that most aspects of immunity are similar in men and women in an athletic population and that the observed differences in a few immune variables are not sufficient to substantially affect URTI incidence. Sex differences in immune function among athletes probably do not need to be considered in future mixed gender studies on exercise, infection and immune function unless the focus is on mucosal immunity or NK cells.

The 'open window' theory is characterised by short term suppression of the immune system following an acute bout of endurance exercise. This window of opportunity may allow for an increase in susceptibility to upper respiratory illness (URI). Many studies have indicated a decrease in immune function in response to exercise. However many studies do not indicate changes in immune function past 2 hours after the completion of exercise, consequently failing to determine whether these immune cells numbers, or importantly their function, return to resting levels before the start of another bout of exercise. Ten male 'A' grade cyclists (age 24.2 +/- 5.3 years; body mass 73.8 +/- 6.5 kg; VO2peak 65.9 +/- 7.1 mL x kg(-1) x min(-1)) exercised for two hours at 90% of their second ventilatory threshold. Blood samples were collected pre-, immediately post-, 2 hours, 4 hours, 6 hours, 8 hours, and 24 hours post-exercise. Immune variables examined included total leukocyte counts, neutrophil function (oxidative burst and phagocytic function), lymphocyte subset counts (CD4+, CD8+, and CD16+/56+), natural killer cell activity (NKCA), and NK phenotypes (CD56dimCD16+, and CD56(bright)CD16-). There was a significant increase in total lymphocyte numbers from pre-, to immediately post-exercise (p < 0.01), followed by a significant decrease at 2 hours post-exercise (p < 0.001). CD4+ T-cell counts significantly increased from pre-exercise, to 4 hours post- (p < 0.05), and 6 hours post-exercise (p < 0.01). However NK (CD16+/56+) cell numbers decreased significantly from pre-exercise to 4 h post-exercise (p < 0.05), to 6 h post-exercise (p < 0.05), and to 8 h post-exercise (p < 0.01O). In contrast, CD56(bright)CD16- NK cell counts significantly increased from pre-exercise to immediately post-exercise (p < 0.01). Neutrophil oxidative burst activity did not significantly change in response to exercise, while neutrophil cell counts significantly increased from pre-exercise, to immediately postexercise (p < 0.05), and 2 hours post-exercise (p < 0.01), and remained significantly above pre-exercise levels to 8 hours post-exercise (p < 0.01). Neutrophil phagocytic function significantly decreased from 2 hours post-exercise, to 6 hours post- (p < 0.05), and 24 hours post-exercise (p < 0.05). Finally, eosinophil cell counts significantly increased from 2 hours post to 6 hours post- (p < 0.05), and 8 hours post-exercise (p < 0.05). This is the first study to show changes in immunological variables up to 8 hours post-exercise, including significant NK cell suppression, NK cell phenotype changes, a significant increase in total lymphocyte counts, and a significant increase in eosinophil cell counts all at 8 hours post-exercise. Suppression of total lymphocyte counts, NK cell counts and neutrophil phagocytic function following exercise may be important in the increased rate of URI in response to regular intense endurance training.

Prolonged exhaustive exercise has a great impact on the immune system of athletes and leads to a transient weakening of the immune system. A host of studies has documented changes of immune parameters in peripheral blood following exercise. Concerning the effect of exhaustive exercise in transplant recipients there is little knowledge at present. We analysed peripheral blood in healthy athletes and transplant recipients who participated in the "Euregio cycling tour 2009" before and immediately after they performed 81 km of cycling that included ascending more than 1800 m in altitude. A full blood count and an automated differential count as well as microarray analysis were performed before, immediately after and one day after exercise in 10 male patients carrying a kidney transplant and in 10 controls matched in age and gender. Comparing the absolute increase in neutrophils in these two groups, we detected that the relative increase in neutrophils was significantly smaller in transplant recipients compared to their corresponding controls after exhaustive exercise. While both groups were comparable in performance, microarray analysis revealed a markedly different pattern of gene expression in transplant recipients compared to their controls. From the 130 genes that were significantly upregulated in controls immediately after exercise, only 12 genes were also upregulated in transplant recipients. 64 different genes were upregulated in transplant recipients only. Our findings may be related to the immunosuppressive medication that the transplant recipients took and therefore it should also be discussed that regular exercise might reduce the need for immunosuppressive medication in transplant recipients.

Physiological and immunological factors contributing to risk for upper respiratory symptoms (URS) in athletic populations remain under investigation. Single nucleotide changes (polymorphisms) in cytokine genes and alterations in associated gene expression may influence risk for URS in some athletes. The aim of this study was to compare the frequency of cytokine gene polymorphisms in athletes with or without a history of frequent URS. Cytokine gene polymorphisms were determined in samples from five previous investigations of immune function in highly-trained athletes (n=170). Participants were classified into two groups based on their self-reported number of episodes of URS in the preceding 12 months. Athletes were classified as healthy (n=82) if they reported < or =2 episodes of URS in the preceding 12 months. Athletes were classified as illness-prone (n=88) if reporting > or =3 episodes of URS. Polymorphisms in Interleukin (IL)-6, IL-8, IL-10, IL-1 receptor antagonist (IL-1ra), IL-2, IL-4 and Interferon(IFN)-gamma were determined using real-time polymerase chain reaction allelic discrimination assays. The distribution of genotype frequencies between the two groups was compared using a Chi-square test and logistic regression was used to model risk for URS as a function of cytokine gene polymorphisms. There was a tendency for IL-6 (chi2 = 5.0, p = 0.08) and IL-4 (chi2 = 4.8, p = 0.09) genotype frequencies to differ between the groups. The IL-6 high-expression genotype was associated with an increased likelihood of > or =3 URS episodes in a 12 month period (odds ratio (OR): 2.87, 95% confidence interval (CI): 1.10-7.53; p = 0.03). The IL-2 high-expression genotype was associated with a tendency for a decreased likelihood of > or =3 URS episodes in a 12 month period (OR: 0.361, 95% CI: 0.124-1.06; p = 0.06). These data suggest cytokine gene polymorphisms may account in part for differences in risk for URS in highly-trained athletes.

Electrical stimulation (ES) is widely used in experimental and clinical settings and shows effects on cellular response to stress; however; mechanisms underlying ES-induced effects are not thoroughly understood. We investigated the Hsp70 response in mouse myoblast derived C2C12 cells to ES at 13V in different groups (A: 12 Hz, 11 min; B: 12 Hz, 90 min; C: 100 Hz, 11 min) and harvested before ES and at 0h, Jh, 4h, 8h and 12h after ES, respectively. Control cells without ES were parallel treated to each stimulated group. Hsp70 expression was determined at protein level by quantitative Western-blot and at mRNA level by real-time PCR, respectively. ES in group A caused a modest biphasic Hsp70 response at mRNA level with a slight increase at protein level. In group B Hsp70 increased significantly (P < 0.01) at mRNA (559%) and protein level (413%), and remained elevated 12 h after ES. In group C the highest Hsp70 mRNA level (14-fold increase, P < 0.01) was observed at 4h after ES with only a moderate increase at protein level (147%, P < 0.05) at 8h after ES. Thus, ES induced distinct Hsp70 responses at both protein and mRNA level, and the characteristics of ES determined the pattern and time course of Hsp70 response in the cultured cells. ES induced Hsp70 response may serve as a common mechanism underlying diverse effects of ES and plays an important role in cellular adaptive response to ES.

Regular exercise is thought to provide protection against age-related cognitive decline and possibly reduce risk of dementias. The mechanisms for the exercise protective effects are not known although changes in inflammatory cytokine levels may be involved. We conducted a systematic review of the literature to assess (1) the effects of exercise on cytokines in the brain, (2) the methodological rigour of studies which have examined these exercise effects and (3) the potential role of regular exercise in reducing the pro-inflammatory cytokine milieu that may contribute to dementia. We also reviewed the effects of exercise on concurrent pro and anti-apoptotic protein expression in the brain as related to cytokine changes. Five databases were searched until January 2010 with an initial 630 articles identified; 61 articles were retrieved of which 10 met study inclusion criteria. Investigations of both acute and chronic (training) exercise were assessed for methodological quality using a modified PEDro scale. Two studies were carried out with human participants and eight with mouse or rat models; studies differed markedly in design and methodological rigour; the types, intensities and durations of exercise, the cytokine and apoptotic proteins measured, and the regions of the brain (or proxy compartments) sampled. Despite variations in design, specific cytokine outcomes, and exercise type, the 10 studies provide limited evidence that acute strenuous exercise increases and exercise training decreases pro-inflammatory cytokines centrally. Two animal studies relate training associated decreases in pro-inflammatory cytokines with improved cognitive function using behavioural assessments such as the Morris maze. Recommendations for the design of future research on exercise, central cytokines, and cognition are offered.

With the discovery of microRNAs (miRNAs), an exceptional means of regulating gene expression was introduced a few years ago. MiRNAs function to inactivate specific messenger RNA transcripts leading to depletion of the corresponding protein, whereby computational studies have shown that about one third of all animal genes might be miRNA targets. Recent publications highlight the involvement of miRNAs in regulating the immune response. The aim of this review is to provide an overview of miRNA biogenesis and function, to illustrate their impact on both the innate as well as the adaptive immune system, to show the regulation of skeletal muscle plasticity and inflammation, and finally to present their possible role within the field of exercise immunology.

Interest in the influence of exercise upon the human white cell population dates back more than a 100 years. Thus, when introducing the third meeting of the International Society of Exercise Immunology in Brussels, Dr. Bente Klarlund-Pedersen noted that Schulte had already described an exercise-induced leukocytosis as early as 1893. However, for much of the following century interest remained strictly clinical, with physicians assessing the possible changes in vulnerability to bacterial and viral diseases that were induced by various forms of physical activity. In the absence of specific remedies, bed rest was a common medical recommendation for infectious disease, and if the patient recovered from the immediate infection there was often a substantial residual loss of physical condition. Army hospitals in particular were thus anxious to know whether recovery would be compromised if physical activity were to be encouraged during convalescence. Prominent concerns of this era were the influence of exercise upon anterior poliomyelitis and viral hepatitis. The paralysis resulting from the anterior poliomyelitis virus was generally localized to body parts that had been active, and it seemed most likely to develop in those who continued to engage in vigorous exercise in the face of early symptoms (46, 57, 119, 120). Data on viral hepatitis also suggested a need for rest in the acute phase of the disease (1, 65, 115, 128), although most authors concluded that in this condition exercise could be resumed during convalescence, provided that the patient was no longer severely jaundiced (5, 32, 136).

The aim of this article is to review current literature on the response of soluble interleukin-6 receptor to exercise and identify a potential role for sIL-6R in skeletal muscle function. We also provide novel data on the impact of eccentric exercise on circulating levels. The aim of the research study was to investigate changes in plasma concentration of soluble interleukin-6 receptor (sIL-6R) and soluble glycoprotein 130 (sgp130) during recovery from exercise-induced muscle damage (EIMD) up to 72 h and their relationship with delayed onset muscle soreness (DOMS) and muscle function. 18 participants attended the laboratory on 4 consecutive days. On the first day, participants completed 6 sets of 10 repetitions of unilateral eccentric-concentric knee flexions at a test speed of 1.05 rad.s(-1) using a Cybex Isokentic dynamometer to induce muscle damage of the hamstrings. Prior to the eccentric exercise bout and each subsequent morning, following an overnight fast, participants had a venous blood sample taken which was centrifuged immediately and plasma frozen at -80 degrees C until later analysis. Plasma IL-6 and sgp130 were unchanged at any time point during recovery but sIL-6R was significantly reduced at 48 h and 72 h post-exercise (p < 0.05). Plasma sIL-6R was correlated with DOMS at 48 h post EIMD (r = 0.45, p < 0.05) and peak muscle torque at 24 h and 48 h following EIMD (r = -.42; p < 0.05; r = -.57; p < 0.01 respectively). Our novel finding that sIL-6R concentrations are decreased 2-3 days following a single bout of EIMD may reflect a regulatory mechanism controlling the influx of different leukocyte subpopulations into damaged tissue, although this needs to be confirmed by future studies. Our data suggests an association between sIL-6R, perception of pain and reduced peak muscle performance post-EIMD but further investigation is warranted to explore this relationship and implications for exercise performance.

Recent research on the effectiveness of training interventions indicates major alterations of hepatic lipid metabolism and suggests a substantial and beneficial adaptation of the liver to regular physical activity in humans. However, while various' data demonstrate the response of the working skeletal muscle to acute exercise and training, considerably less is known about the molecular events in the liver during and after increased physical activity. Here we discuss recent studies performed in rodents, that elucidate the acute hepatic response to one single bout of exercise with particular emphasis on stress response-related pathways. The acute transcriptional response to one exercise bout comprises three-times more hepatic transcripts than those expressed in soleus muscle, with a significantly more pronounced up- or downregulation of hepatic genes. Evaluation of the affected pathways shows that the liver responds to acute exercise with a rapid activation of the mitogen-activated protein kinase (MAPK) signalling pathway, of the p53 protein, and of interleukin (IL)-6-type cytokine signalling pathways, resulting in a marked transcriptional upregulation of stress response genes (e.g., transcription factors of the Fos/Jun-family, growth arrest and DNA damage (GADD)45gamma, and p53-target genes) and genes typically induced by energy depletion, e.g., insulin-like growth factor binding protein (IGFBP)-1, peroxisome proliferator-activated receptor coactivator (PGC)1alpha. One explanation for the marked differential expression of hepatic genes immediately after exercise is the induction of energetic stress. After non-exhaustive exercise energy depletion predominantly occurs in the liver not as much in the working muscle, and during exercise, the liver is exposed to altered concentrations of insulin and glucagon in the portal vein. Furthermore, lower plasma glucose levels post-exercise are related to increased expression levels of stress response genes. It appears that the unique function of the liver to supply glucose for the working muscle renders this organ especially susceptible for exercise-induced cellular stress that leads to the marked induction of defense adaptations. These results give rise to the question whether these molecular events are linked not only to stress defense but to the metabolic adaptations of the liver to exercise.