Maree Gleeson

Salivary IgA levels and infection risk in elite swimmers

UNLABELLED The effects of exercise on the immune system has been shown to be dependent on the level of fitness of the subjects, the degree of intensity, and the duration of the exercise. A reduction in salivary IgA levels occurs after individual sessions of exercise. PURPOSE The purpose of this study was to assess the relationship between changes in salivary IgA and training volume, psychological stress, and infection rates in a cohort of 26 elite swimmers over a 7-month training period and to compare the changes with a group of 12 moderately exercising controls. METHODS Salivary IgA concentrations were measured by an electroimmunodiffusion. Exercise gradings were assessed by a standardized aerobic-anaerobic rating system. Psychological stress/anxiety was evaluated by the Spielberger State-Trait Anxiety Inventory. Infections were physician-verified. RESULTS Salivary IgA levels showed an inverse correlation with the number of infections in both elite swimmers and moderately exercising control subjects. The pretraining salivary IgA levels in swimmers were 4.1% lower for each additional month of training and 5.8% lower for each additional infection. The posttraining salivary IgA levels in swimmers were not significantly correlated with infection rates but were 8.5% lower for each additional 1 km swum in a training session and 7.0% lower for each additional month of training. The number of infections observed in the elite swimmers was predicted from regression models by the preseason (P = 0.05) and the mean pretraining salivary IgA levels (P = 0.006). The trends in pretraining salivary IgA levels over the 7-month season, calculated as individual slopes of pretraining IgA levels over time, were also predictive of the number of infections (P = 0.03) in the swimmers. CONCLUSIONS These results indicate that measurement of salivary IgA levels over a training season may be predictive for athletes at risk of infection.

C-reactive protein: A critical review

&NA; We have reviewed the literature to determine the value of C‐reactive protein (CRP) measurements in the diagnosis and management of a wide range of conditions. CRP levels are of value in 6 clinical situations: (a) monitoring the response to antibiotic treatment in patients with known bacterial infections, (b) in obstetric patients with premature rupture of membranes, a rise in CRP can give early warning of intrauterine infections, (c) differentiation between active disease and infections in patients with systemic lupus and ulcerative colitis where the level of response to active disease has been previously established, (d) as a measure of disease activity and response to disease‐modifying drugs in rheumatoid arthritis, (e) early detection of complications in postoperative patients, (f) in differentiating between infection and graft‐versus‐host‐disease in bone marrow transplant patients. CRP levels have been used in an attempt to differentiate between bacterial and viral infections in various clinical situations, however the published literature does not support this role.

The effect on immunity of long‐term intensive training in elite swimmers

The impact of long‐term training on systemic and mucosal immunity was assessed prospectively in a cohort of elite swimmers over a 7‐month training season in preparation for national championships. The results indicated significant suppression (P < 0.05) of serum IgA. IgG and IgM and salivary IgA concentration in athletes associated with long‐term training at an intensive level. There was also a trend towards lower IgG2 subclass levels in serum in athletes compared with controls (P= 0.07). There were no significant changes in numbers or percentages of B or T cell subsets, but there was a significant fall in natural killer (NK) cell numbers and percentages in athletes over the training season (P < 0.05). After individual training sessions there was a significant decrease in salivary IgA levels for athletes compared with controls (P= 0.02). In athletes there was a downward trend in salivary IgA levels over the 7‐month training period in both the pre‐exercise (P= 0.06) and post‐exercise samples (P= 0.04). There were no significant trends in salivary IgG levels over the study period in either athletes or controls. The only significant change in salivary IgM levels was an increase in detection rate in the pre‐competition phase in athletes (P= 0.03). The study suggests that training of elite athletes at an intensive level over both short‐ and long‐time frames suppresses both systemic and mucosal immunity. Protracted immune suppression linked with prolonged training may determine susceptibility to infection, particularly at times of major competitions.

Exercise effects on mucosal immunity

The present review examines the effects of exercise on mucosal immunity in recreational and elite athletes and the role of mucosal immunity in respiratory illness. Habitual exercise at an intense level can cause suppression of mucosal immune parameters, while moderate exercise may have positive effects. Saliva is the most commonly used secretion for measurement of secretory antibodies in the assessment of mucosal immune status. Salivary IgA and IgM concentrations decline immediately after a bout of intense exercise, but usually recover within 24 h. Training at an intense level over many years can result in a chronic suppression of salivary immunoglobulin levels. The degree of immune suppression and the recovery rates after exercise are associated with the intensity of exercise and the duration or volume of the training. Low levels of salivary IgM and IgA, particularly the IgA1 subclass, are associated with an increased risk of respiratory illness in athletes. Monitoring mucosal immune parameters during critical periods of training provides an assessment of the upper respiratory tract illness risk status of an individual athlete. The mechanisms underlying the mucosal immune suppression are unknown.

Epstein-barr virus reactivation and upper-respiratory illness in elite swimmers

PURPOSE The aim of this study was to investigate the relationships between latent viral shedding of Epstein-Barr virus (EBV) in saliva, upper-respiratory illness, and mucosal immune suppression in a cohort of highly trained swimmers undertaking intensive training. METHODS Saliva was collected before selected training sessions from 14 elite male swimmers during a 30-d period of intensive training. Prior infection with EBV was determined by EBV antibody serology. Salivary IgA concentrations were measured by enzyme linked immunosorbent assay (ELISA), and EBV viral shedding (EBV-DNA) was detected by polymerase chain reaction (PCR). Symptoms of upper-respiratory illness were recorded daily. RESULTS Eleven swimmers (79%) were seropositive for prior EBV infection. Seven EBV seropositive swimmers (64%) had EBV-DNA detected during the study period. Upper-respiratory symptoms (URS) were reported in six of seven swimmers in whom EBV-DNA was detected and in three of four swimmers with no EBV-DNA detection. No URS were reported in the EBV seronegative swimmers. There was a statistically significant relationship between EBV serology status and URS (P = 0.027). EBV-DNA was detected in saliva before the appearance of URS. Salivary IgA levels were significantly lower immediately before the URS (P = 0.01) compared with subsequent peak IgA levels and declined to pre-URS levels on average 11 d after the first appearance of URS. CONCLUSIONS The time course of appearance of EBV-DNA in relation to URS suggests latent viral EBV shedding may be a contributing factor in the URS. The low levels of salivary IgA detected before the URS indicated transient mucosal immune suppression in the study cohort. The viral shedding may alternatively be a reflection of the altered immune control mechanisms that occur in response to intensive exercise and unrelated to the URS.

Cytokine responses and sudden infant death syndrome: genetic, developmental, and environmental risk factors

Despite the success of the campaigns to reduce the risk of sudden infant death syndrome (SIDS), it still remains the major cause of postneonatal mortality. The incidence of SIDS is higher among ethnic groups in which there are also high incidences of serious infectious diseases. The risk factors for SIDS parallel those for susceptibility to infection, and recent data have provided evidence to support the mathematical model of the common bacterial toxin hypothesis. One current hypothesis for the etiology of SIDS is that the deaths are a result of overwhelming proinflammatory responses to bacterial toxins; as in inflammatory responses to sepsis, cytokines, induced by bacterial toxins, cause physiological changes leading to death. The genetic, developmental, and environmental risk factors for SIDS are reviewed in relation to colonization by potentially harmful bacteria and the inflammatory responses induced in the nonimmune infant to microorganisms or their products.

Modifiers of the human mucosal immune system.

This review focuses on saliva as a measure of mucosal immunity in man. The review will cover studies of parameters that modify the early ontogeny patterns of mucosal immunity and the impact of infections and physiological variables on the human mucosal immune response. The most significant modifiers of human mucosal immunity are events that occur in the neonatal maturation period and, later in life, the interplay between the immune system and the neuroendocrine systems. IgA antibodies are the predominant isotype involved in the human mucosal immune response and are important for protection at mucosal surfaces. The level of IgA in mucosal secretions is modified by antigenic stimulation as well as by many physiological variables. Studies have also revealed that IgM plays a significant immunoregulatory role at mucosal surfaces, particularly during episodes of infection or stress. The detection patterns of IgD in saliva of neonates suggests a role for IgD in the initial maturation process of mucosal immunity. The role of IgG at mucosal surfaces is unclear and although IgG may play a compensatory role in IgA deficiency, the detection of high levels of IgG in saliva appears to be associated with periods of increased membrane permeability.

Clinical investigation of athletes with persistent fatigue and/or recurrent infections

Objective: To investigate whether underlying medical conditions contribute to the fatigue and high incidence of infections that can occur during repeated intense training. Method: Forty one competitive athletes (22 male, 19 female) with persistent fatigue and/or recurrent infections associated with performance decrements had a thorough medical examination and a series of clinical investigations to identify potential medical causes. Results: Conditions with the potential to cause fatigue and/or recurrent infections were identified in 68% of the athletes. The most common were partial humoral immune deficiency (28%) and unresolved viral infections (27%). Non-fasting hypoglycaemia was common (28%). Other conditions included allergic disease (15%), new or poorly controlled asthma (13%), upper airway dysfunction (5%), sleep disorders (15%), iron depletion (3%), and one case of a thyroid disorder. A positive antinuclear antibody was detected in 21% of the athletes, without any clinical evidence of autoimmune disorders. Evidence of Epstein-Barr virus reactivation was detected in 22% of the athletes tested. Conclusions: Athletes with recurrent infections, fatigue, and associated poor performance may benefit from a thorough investigation of potentially reversible underlying medical conditions, especially when these conditions cause disruption to training and competition. Unresolved viral infections are not routinely assessed in elite athletes, but it may be worth considering in those experiencing fatigue and performing poorly.

SALIVARY IGA SUBCLASSES AND INFECTION RISK IN ELITE SWIMMERS

The concentrations of total IgA, IgA1 and IgA2 were measured in saliva collected from 25 elite swimmers in the early and late phases of a 7 month training season and compared with the number of respiratory infections during the season. The IgA1 concentrations in the early phase of the training season were significantly associated (P = 0.01) with the number of respiratory infection episodes during the training season. The lower the concentration of IgA1, the greater the number of infection episodes. Swimmers with four or more infections during the training season had significantly lower salivary IgA1 concentrations than those with less than four infection episodes (P = 0.01). The proportion of IgA1 in the saliva of the elite swimmers (80%) was higher than for normal non‐exercising adults (60%). A small proportion of athletes had salivary IgA2 concentrations below the detection limit of the assay and the mean concentration of IgA2 was significantly lower than the concentrations for a normal adult population (P = 0.01). This study suggests that measurement of IgA subclasses, in particular IgA1, at the commencement of a training season may predict infection risk in elite swimmers.

Reversal in fatigued athletes of a defect in interferon γ 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) γ from blood CD4 positive T cells. After one month of daily capsules containing 2 × 1010 colony forming units of L acidophilus, secretion of IFNγ from T cells had increased significantly (p  =  0.01) to levels found in healthy control athletes. A significant (p  =  0.03) increase in salivary IFNγ 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 IFNγ concentration. Conclusion: This is the first evidence of a T cell defect in fatigued athletes, and of its reversal following probiotic therapy.