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The impact of psychological stress on immune function in the athletic population.

In many ways, the physiological and immune consequences of acute bursts of physical exercise parallel the effect of an acute psychological stressor. Similarly, the net effects of endurance training resemble chronic psychological stress, whereas the physiological milieu associated with overtraining resembles that of melancholic depression. We suggest that the prolonged psychological stress often associated with athletic training and competition may make athletes more vulnerable to the negative health effects of training. Furthermore, a relationship between anxiety and life events on susceptibility to injury is well documented. Individual differences in self-confidence and self-esteem are also known to relate to the occurrence of injury as well as recovery from injury. We suggest that these two observations may be linked. It is the purpose of this paper to review the most recent evidence that psychological stress does impact upon the balance of the immune system in such a way as to be relevant to health outcomes and that the athletic population, in particular those with low self-esteem, may be especially vulnerable due to the probable synergistic effects of both physical and psychological stress.

Athletic Injuries↗

Prolonged suppression of the innate immune system in the horse following an 80 km endurance race.

REASONS FOR PERFORMING STUDY: An increased susceptibility to bacterial and viral infections of the respiratory tract, which results in a loss of performance, has been reported in racehorses. Much research has focused on the influence of high-intensity exercise of a short duration on immune system function in horses, but scant attention has been given to prolonged endurance exercise as an immune modulator. OBJECTIVES: The objective of this study was to evaluate the effect of an 80 km endurance race on the monocyte and neutrophil oxidative burst, serum cortisol, glutamine and plasma glucose concentrations in 8 endurance-trained horses (mean +/- s.d. age 9.4 +/- 2.2 years). METHODS: Blood samples were drawn from the horses prior to and following an 80 km ride. RESULTS: Mean time for completion of the 80 km race was 306 +/- 40 mins. Immediately post race mean serum cortisol concentration, blood monocyte and neutrophil counts were higher and blood lymphocyte counts and plasma glucose concentration were lower compared with prerace values (P < 0.05). Neutrophil and monocyte oxidative burst activity decreased following the race and had not regained prerace values after 3 days of rest (P < 0.05). CONCLUSIONS: The present study indicates that long duration exercise in horses has a negative impact on the function of the innate immune system that lasts several days post race. Precise mechanisms instigating the fall in innate immune system function are unclear and multifactorial, but may be attributed, at least in part, to a high serum cortisol response during very prolonged exercise. POTENTIAL CLINICAL RELEVANCE: A prolonged bout of exercise results in a long-term suppression of the innate immune system function in horses which may, in part, account for the observed increase of infectious episodes in horses during training.

Animals↗

Immune function in Swedish élite orienteers.

During 1979-1992 an increased frequency of sudden unexpected cardiac death (SUD) occurred among young male Swedish élite orienteers. Subacute-to-chronic myocarditis was found in 12/16 (75%) at autopsy and Chlamydia pneumoniae, or a cross-reacting agent, was suspected on the basis of diagnostic tests performed. Because myocarditis is an infrequent cause of SUD and clusters of SUD are rare, whereas Chlamydia pneumoniae infections are ubiquitous and seldom cause severe myocarditis, 119 top ranked élite orienteers (67 males and 52 females) and 36 highly trained male middle-distance runners and cross-country skiers, serving as controls, underwent immunologic screening in an effort to reveal possible immune dysfunction. Except for two orienteers and one runner/skier who showed genetic C3-deficiency or IgA-deficiency, the results showed no significant differences between the orienteers and controls with respect to immunoglobulin levels, complement activation, lymphocyte subsets, including activated T lymphocytes, and sIL-2r-alpha. IL-1 beta, IL-6, TNF-alpha, and sCD8, tested in the orienteers only, were normal. However, IFN-gamma was significantly higher in controls than in orienteers, who showed normal levels, whereas the orienteers had increased sELAM-1 and sICAM-1 levels. Finally, sIL-2 receptor-alpha was similarly elevated in orienteers and controls. We conclude that, with the tests employed, no immunologic disturbance could be revealed in the orienteers that may potentially have increased their susceptibility to myocarditis and SUD.

Adolescent↗

Can community health workers screen under 5 yr children with computer program.

EKALAVYA computer program aims at high risk screening of under 5 children in Primary Health Centers by Community Health Workers (CHWs) simulating existing programs like CSSM, ICDS etc. This integrates many common symptoms like fever, respiratory, diarrhea, convulsions etc. along with health promotional aspects like growth, immunization etc. at Community Health Workers skills level. EKALAVYA program was user friendly for CHWs who were trained in 2-3 weeks. CHWs with computer guidance were compared with clinical evaluation of Research Team in 96 pediatric OPD cases in a teaching institution. Overall concordance was 91.66%. Symptom wise and severity wise analysis also showed good concordance. The study also indicated training and programme errors which could be easily corrected. EKALAVYA Program is now ready for field trial in PHCs for the guidance of CHWs in decision making.

Child Health Services↗

Validation of in silico prediction by in vitro immunoserological results of fine epitope mapping on citrate synthase specific autoantibodies.

In silico antibody-antigen binding predictions are generally employed in research to rationalize epitope development. These techniques are widely spread despite their technical limitations. To validate the results of these bioinformatic calculations evidence based comparative in vitro studies are necessary. We have used a well-conserved mitochondrial inner membrane antigen-citrate synthase to develop a model for comparative analysis of the predicted and the immunoserologically verified epitopes of circulating autoantibodies. Epitopes were predicted using accepted tools: the GCG Wisconsin package and TEPITOPE 2000. An overlapping multipin ELISA assay--covering 49% of the citrate synthase molecule--was developed to map autoantibody epitopes of individuals (healthy, systemic autoimmune, and heart transplanted) in different immunopathological conditions. From the 40 synthesized decapeptides 34 were predicted in silico and 27 were validated in vitro. Thirty-two percent of epitopes were recognized by majority of sera 47% by at least one sera. False positive predictions were 21%. There was major difference in the recognized epitope pattern under different immunopathological conditions. Our results suggest that special databases are needed for training and weighing prediction methods by clinically well-characterized samples, due to the differences in the immune response under different health status. The development of these special algorithms needs a new approach. A high number of samples under these special immunological conditions are to be mapped and then used for the "fine tuning" of different prediction algorithms.

Amino Acid Sequence↗

Reversal in fatigued athletes of a defect in interferon gamma secretion after administration of Lactobacillus acidophilus.

BACKGROUND: Fatigue and impaired performance in athletes is well recognised and has been loosely linked to "overtraining". Reduced concentration of IgA in the saliva and increased shedding of Epstein Barr virus (EBV) have been associated with intense training in elite athletes. OBJECTIVE: To determine whether athletes presenting with fatigue and impaired performance had an immune defect relevant to defective containment of EBV infection, and whether a probiotic preparation (Lactobacillus acidophilus) shown to enhance mucosal immunity in animal models could reverse any detected abnormality. RESULTS: The fatigued athletes had clinical characteristics consistent with re-activation of EBV infection and significantly (p = 0.02) less secretion of interferon (IFN) gamma from blood CD4 positive T cells. After one month of daily capsules containing 2 x 10(10) colony forming units of L acidophilus, secretion of IFNgamma from T cells had increased significantly (p = 0.01) to levels found in healthy control athletes. A significant (p = 0.03) increase in salivary IFNgamma concentrations in healthy control athletes after the one month course of L acidophilus demonstrated in man the capacity for this probiotic to enhance the mucosal IFNgamma concentration. CONCLUSION: This is the first evidence of a T cell defect in fatigued athletes, and of its reversal following probiotic therapy.

Adolescent↗

Wound contamination and postoperative infection. A review.

The risk of postsurgical infection is closely related to the type of operation performed. Wound sampling by Raahave's velvet pad method shows that operation wounds harbour ordinary aerobic and anaerobic commensals after incision (exogenous flora). When bacteria-containing viscera are opened or found perforated, bacterial densities increase significantly before wound closure (endogenous flora). Contamination level justifies the criteria for use of wound class, i.e. clean, potentially contminated, contaminated and dirty. There is a dose-response relationship between the density of bacteria during operation and postsurgical wound sepsis. The median infective dose of aerobic and anaerobic bacteria is 4.6 x 10(5) CFU x cm-2 wound. The surgeon opens up tissue planes which are primarily sterile and breaks natural barriers. However, using a trained technique, the surgeon should be able to control wound contamination safely throughout the operation. Although hos immunity and tissue resistance intervene between contamination and infection, the magnitude of contamination seems crucial. It ought to be axiomatic by now that reducing bacterial contamination reduces infection.

Anti-Bacterial Agents↗

Post-traumatic stress disorder among Special Forces Vietnam veterans.

Fifty-seven Special Forces Vietnam Veterans were studied to determine if special selection and rigorous training affected the frequency and pattern of predictors of post-traumatic stress disorder (PTSD). No absolute immunity to PTSD was conferred. Frequency (25%) and predictors of PTSD were similar to those reported for other groups of Vietnam Veterans. Symptoms of PTSD were associated with poorer pre-service relationships, being wounded, being wounded after return from R&R, having friends missing in action, feeling guilt over the death of a friend, lack of emotional preparation to leave the unit or service, and failure to discuss feelings upon return from Vietnam.

Humans↗

Current perspective on exercise immunology.

By far, the most important finding that has emerged from exercise immunology studies is that positive immune changes take place during each bout of moderate physical activity. Over time, this translates to fewer days of sickness with the common cold and other upper respiratory tract infections. This is consistent with public health guidelines urging individuals to engage in near-daily physical activity of 30 minutes or more. Risk of upper respiratory tract infections can increase when athletes push beyond normal limits. The infection risk is amplified when other factors related to immune function are present, including exposure to novel pathogens during travel, lack of sleep, severe mental stress, malnutrition, or weight loss. Many components of the immune system exhibit adverse change after prolonged, heavy exertion lasting longer than 90 minutes. These immune changes occur in several compartments of the immune system and body (eg, the skin, upper respiratory tract mucosal tissue, lung, blood, and muscle). During this "open window" of impaired immunity (between 3 and 72 hours, depending on the immune measure), viruses and bacteria may gain a foothold, increasing the risk of subclinical and clinical infection. In general, if symptoms are from the neck up, moderate exercise is probably acceptable (and some researchers would argue even beneficial) when an athlete is sick, whereas bed rest and a gradual progression to normal training are recommended when the illness is systemic.

Attitude of Health Personnel↗

The effects of biofeedback-assisted relaxation on cell-mediated immunity, cortisol, and white blood cell count in healthy adult subjects.

The effect of biofeedback-assisted relaxation on cell-mediated immunity, cortisol, and white blood cell count was investigated in healthy adults under low-stress conditions. Fourteen subjects were trained with biofeedback-assisted relaxation for 4 weeks, while 17 subjects were controls. The group trained in relaxation techniques showed increased blastogenesis, decreased white blood cell count, due to decreased neutrophils, and no change in cortisol in comparison to the control group. Subjects with lower initial anxiety scores and forehead muscle tension levels showed larger increases in blastogenesis and larger decreases in neutrophils than subjects with higher initial anxiety and muscle tension levels.

Adult↗

Immunization and the chiropractor-patient interaction: a Western canadian study.

OBJECTIVE: To explore how the topic of vaccination arises during interactions between chiropractors and their patients, the advice that is given to patients, and the factors that influence the opinions of the chiropractors. METHODS: Data were collected in semistructured interviews with a purposeful sample of chiropractors in Calgary, Canada. Data were analyzed using qualitative content analysis and constant comparison. Participants were chiropractors who had participated in a postal survey of immunization-related beliefs and behaviors and who consented to contact for further study. RESULTS: Data redundancy was attained after 14 interviews were complete. Immunization arose in clinical encounters by both indirect (provision of reference materials and/or posting of media stories in clinic waiting rooms) and direct communication. Direct communications were most commonly patient initiated and were prompted by media reports, clinic waiting room material, or patient perceived adverse reactions; however, they were also initiated by the chiropractors, particularly if they were seeing young children with their parents. For some chiropractors, the emphasis was on providing information of a negative, antivaccination nature; others referred clients to physicians and nurses. Factors that influenced their opinions included their chiropractic training, philosophy of health and illness, and self or important others having experienced negative reactions that were perceived to result from immunization. CONCLUSIONS: Both patients and chiropractors initiate discussions on immunization in practice, with many chiropractors using indirect stimuli to open the topic. Doctors of chiropractic in this particular sample were heterogeneous with respect to the information provided to patients. However, study findings may not be generalizable outside Canada.

Attitude of Health Personnel↗

Tissue trauma: the underlying cause of overtraining syndrome?

An athlete who trains intensely, yet consistently underperforms, is considered to be suffering from overtraining syndrome (OTS). OTS is a complex state that involves a large variety of signs and symptoms. Symptoms include changes in mood or behaviour, decreases or increases in concentration of different blood molecules, and alterations in immune function. Although several hypotheses have been proposed, each only explains a selective aspect of OTS. Presently, the sole agreement is that OTS is associated with excessive training and insufficient rest and recovery. The hypothesis proposed in this paper suggests that excessive training/competing causes repetitive tissue trauma, either to muscle and/or connective tissue and/or to bony structures, and that this results in chronic inflammation. It is further proposed that traumatized tissue synthesizes a group of inflammatory molecules, cytokines. Cytokines have been shown to coordinate the different systems of the body to promote recovery. Suggestions are made to detect, prevent, and rehabilitate the overtrained athlete.

Affective Symptoms↗

Immune function in marathon runners versus sedentary controls.

Marathon runners (N = 22) who had completed at least seven marathons (X +/- SEM = 23.6 +/- 5.7) and had been training for marathon race events for at least 4 yr (12.3 +/- 1.3) were compared with sedentary controls (N = 18). Although the two groups were of similar age (38.7 +/- 1.5 and 43.9 +/- 2.2 yr, respectively) and height, the marathon runners were significantly leaner and possessed a VO2max 60% higher than that of the controls. Neutrophil counts tended to be lower in the group of marathoners, while other leukocyte and lymphocyte subsets were similar to controls. Mitogen-induced lymphocyte proliferation did not differ between groups. Natural killer cell cytotoxic activity (NKCA) was significantly higher in the marathoners versus controls (373 +/- 38 vs 237 +/- 41 total lytic units, respectively, a 57% difference, P = 0.02). For all subjects combined (N = 40) and within the group of marathon runners (N = 22), percent body fat was negatively correlated with NKCA (r = -0.48, P = 0.002; r = -0.49, P = 0.019, respectively), and age was negatively correlated with Con A-induced lymphocyte proliferation (r = -0.41, P = 0.009; r = -0.53, P = 0.011, respectively). These data indicate that NKCA but not mitogen-induced lymphocyte proliferation is higher in marathon runners relative to sedentary controls.

Adult↗

Current challenges and future expectations in exercise immunology: back to the future.

The immune system response to exercise is multifaceted, depending on the nature of exercise. The motivation behind recent research on the immune response to exercise comes from four basic directions: (i) keeping competitive athletes healthy, based on the perception that athletes are susceptible to infectious illness during intense training and competition; (ii) community interest in health promotion, based on the beneficial effect of exercise in lessening the risk of other lifestyle-associated diseases such as heart disease; (iii) use of exercise as adjunct therapy to improve patient functional capacity in certain diseases such as acquired immune deficiency syndrome (AIDS) and cancer; and (iv) work in the field of psychoneuroimmunology showing significant interaction between the neuroendocrine and immune systems, and the role of lifestyle factors in modulating immune function. Future work in exercise immunology will focus on topics such as: identifying the role of neuroendocrine factors in regulating the immune response to exercise; understanding the effects and appropriate type of moderate exercise in patients with diseases which involve the immune system; and possible long-term role of regular exercise in preventing diseases such as cancer, or the decline in immune function which accompanies the aging process.

Aging↗

Effect of moderate exercise on immune senescence in men.

The purpose of this study was to examine the relationship between active compared to inactive lifestyles and immunocompetence in men. Subjects, all male volunteers, regularly exercising moderately were separated into three age groups: young (20-39 years), middle-aged (40-59 years) and elderly (more than 60 years). Age-matched sedentary male subjects served as controls in each group. Immunological assessments were, total leucocyte count, lymphocyte subpopulation counts, natural killer cell activity and neutrophilic phagocytosis. Total leucocyte and T-cell (CD3+) counts were not significantly different among the groups. Among T-cell subsets, there was a slight increase in helper T-cell (CD3+CD4+) and a decrease in cytotoxic/suppressor T-cell (CD3+CD8+) concentrations in the older sedentary subjects, resulting in an age-associated significant increase in the CD4:CD8 ratio among those control groups. However, among the exerciser groups, no such increase and decrease in the T-cell subpopulations or an age-related increase of the CD4:CD8 ratio were observed. Considering the components of innate immunity, the concentration of NK-cells (CD16+CD56+) significantly increased in the elderly exercisers, compared to that of the age-matched control subjects, or of the young group. The phagocytotic activity of neutrophils showed an age-associated decline, but of lesser degree in the elderly exercisers than in the elderly controls. Taken together, these results suggest that habitual and moderate training in later life is associated with a lesser age-related decline in certain aspects of circulating T-cell function and innate immunity.

Adult↗

Construction of a new predictive model in head and neck squamous cell carcinoma based on the investigation of extracellular matrix-associated genes.

A key aspect influencing immune cell infiltration is the composition of the extracellular matrix (ECM). Therefore, investigating the association between ECM-associated proteins and immune cell infiltration is key for the identification of new biomarkers to distinguish 'immune-hot' solid tumors and predict patient prognosis. A total of 513 head and neck squamous cell carcinoma (HNSCC) cases as training samples from The Cancer Genome Atlas and an additional 270 as testing samples from the Gene Expression Omnibus were obtained for use in the present study. Using a single-sample Gene Set Enrichment Analysis method, the 513 training samples were divided into Cluster 1 and Cluster 2. Subsequently, the present analysis uncovered 1,573 differentially expressed genes distinguishing the two clusters. After performing an intersection analysis with 751 ECM-associated genes, 103 differentially expressed ECM-associated genes were identified. Least absolute shrinkage and selection operator-Cox and multivariate Cox regression analyses were employed to identify candidate ECM risk genes (P<0.05) and to construct a predictive model. Finally, a nomogram and a three gene (cerebellin 2, galectin-10 and cathepsin G) predictive model were developed. Therefore, the present prognostic risk score model can evaluate the immune infiltration, predict the prognosis of HNSCC, and potentially guide more personalized immunotherapy interventions.

extracellular matrix↗

Risk of transmission of hepatitis B virus through childhood immunization in northwestern China.

Transmission of bloodborne pathogens by means of unsafe injection practices is a significant public health problem in developing countries. Although the overall proportion for immunization is low among injections, unsafe immunization practices affect mostly infants, a population with an increased likelihood of becoming hepatitis B virus carriers. This study estimated the prevalence of unsafe injection among vaccinators working at the peripheral level in northwestern China and the risk of HBV infections among infant vaccinees, and analyzed factors contributing to the most prevalent unsafe practice: the reuse of a non-sterilized reusable syringe among infants. A knowledge-attitude-practice survey was conducted in which 180 peripheral vaccinators selected by multi-stage cluster sampling in each of four provinces and one autonomous region completed a self-administered questionnaire. The lack of observational data for assessing the validity of the self-reported practices made the study prone to systematic respondent bias that may have skewed the results towards underestimation of unsafe practices. The minimum estimate of the percentage of peripheral vaccinators reusing a syringe and/or needle without sterilization between infants was 7.2-55.0%, whereas the percentage of those disposing of used disposable syringes and needles inappropriately was 8.9-23.3% by province. According to a model-based estimate, the annual number of HBV infections among 100,000 fully immunized children due to unsafe immunization injection was at least 135-3120. An insufficient supply of syringes and the attitude to justify reuse were significantly associated with the unsafe reuse of a reusable syringe in most part of the area studied. Introduction of auto-disable syringes may contribute to curb the unsafe practices, but the development of safe collection and disposal procedures for used syringes and needles is prerequisite. Sufficient supply of equipment as well as training, supervision, and monitoring targeting specifically on the risk behaviors and concerned attitudes are essential for behavior changes among the vaccinators.

Blood-Borne Pathogens↗

Interdisciplinary research: noradrenergic regulation of adaptive immunity.

To understand the complexity of mechanisms involved in the regulation of adaptive immunity by the sympathetic neurotransmitter norepinephrine and adrenergic receptor stimulation, there must be a rich history of basic science and clinical findings upon which to form hypotheses for testing, as well as a rich supply of individuals trained in two or more disciplines. This review is intended to offer a tour of the past, present, and future discoveries that have been made in the area of adrenergic regulation of adaptive immunity, as well as share a vision of how our field of study will progress years from now, given that every individual who contributes to the interdisciplinary nature of our research is valued. And finally, this review will discuss how the lessons from the past can help us to attain a vision of interdisciplinary research for the future.

Adaptation, Physiological↗