Acute psychological stress induces short-term variable immune response.

In spite of advances in understanding the cross-talk between the peripheral immune system and the brain, the molecular mechanisms underlying the rapid adaptation of the immune system to an acute psychological stressor remain largely unknown. Conventional approaches to classify molecular factors mediating these responses have targeted relatively few biological measurements or explored cross-sectional study designs, and therefore have restricted characterization of stress-immune interactions. This exploratory study analyzed transcriptional profiles and flow cytometric data of peripheral blood leukocytes with physiological (endocrine, autonomic) measurements collected throughout the sequence of events leading up to, during, and after short-term exposure to physical danger in humans. Immediate immunomodulation to acute psychological stress was defined as a short-term selective up-regulation of natural killer (NK) cell-associated cytotoxic and IL-12 mediated signaling genes that correlated with increased cortisol, catecholamines and NK cells into the periphery. In parallel, we observed down-regulation of innate immune toll-like receptor genes and genes of the MyD88-dependent signaling pathway. Correcting gene expression for an influx of NK cells revealed a molecular signature specific to the adrenal cortex. Subsequently, focusing analyses on discrete groups of coordinately expressed genes (modules) throughout the time-series revealed immune stress responses in modules associated to immune/defense response, response to wounding, cytokine production, TCR signaling and NK cell cytotoxicity which differed between males and females. These results offer a spring-board for future research towards improved treatment of stress-related disease including the impact of stress on cardiovascular and autoimmune disorders, and identifies an immune mechanism by which vulnerabilities to these diseases may be gender-specific.

Biochemical markers of possible immunodepression in military training in harsh environments.

Prolonged, exhaustive exercise frequently leads to an increased incidence of upper respiratory tract illness (URTI) which is linked to transient immunodepression. We investigated potential biochemical markers of stress and fatigue, and URTI symptoms as a surrogate of immunodepression, in US Marines undergoing intensive winter training at altitude. Selected plasma amino acids and leptin (p[Lep]) were measured as possible markers of fatigue and immunodepression, together with nonesterified fatty acids (p[NEFA]) and total antioxidant capacity (p[TAC]). Changes were observed in plasma free tryptophan (p[FT]), p[Gln], p[Lep], p[NEFA], p[TAC] but not branched chain amino acids (p[BCAA]). p[FT] decreased markedly. Resting p[Gln] decreased overall after one month at altitude. p[Gln] routinely decreases 1-2 hrs after prolonged exercise. Importantly, we observed early morning decreases in p[Gln], suggesting a cumulative effect of prolonged activity, stress, and fatigue. Concomitantly, individuals with highest illness scores had the greatest p[Gln] decrease: low p[Gln] may therefore be associated with a diminished stress tolerance.

Effects of training and strenuous exercise on hematologic values and peripheral blood leukocyte subsets in racing sled dogs.

OBJECTIVE: To determine the effects of training and sustained submaximal exercise on hematologic values in racing sled dogs. DESIGN: Cohort study. ANIMALS: 39 Alaskan sled dogs bred for endurance racing. Procedures-Blood samples were collected prior to initiation of a 7-month training regimen (n=39), after completion of the training regimen (19), and after completion of an 1,100-mile race (9), and a CBC, differential cell count, and flow cytometry for leukocyte surface antigens were performed. RESULTS: Both training and exercise caused significant decreases in PCV and hemoglobin concentration and significant increases in total WBC count. In contrast, training and exercise were not found to have significant effects on absolute numbers or fractions of CD4+ or CD8+ lymphocytes, other than a significant increase in the fraction of CD8+ lymphocytes associated with training. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that training and exercise induced changes in several hematologic values in racing sled dogs. Extracellular fluid volume expansion was the likely explanation for the training-induced decrease in PCV, and acute blood loss secondary to gastrointestinal tract bleeding was likely responsible for the decrease in PCV associated with acute exercise.

Disparate LDL phenotypic classification among 4 different methods assessing LDL particle characteristics.

BACKGROUND: Our study seeks to clarify the extent of differences in analytical results, from a clinical perspective, among 4 leading technologies currently used in clinical reference laboratories for the analysis of LDL subfractions: gradient gel electrophoresis (GGE), ultracentrifugation-vertical auto profile (VAP), nuclear magnetic resonance (NMR), and tube gel electrophoresis (TGE). METHODS: We collected 4 simultaneous blood samples from 40 persons (30 males and 10 females) to determine LDL subclasses in 4 different clinical reference laboratories using different methods for analysis. LDL subfractions were assessed according to LDL particle size and the results categorized according to LDL phenotype. We compared results obtained from the different technologies. RESULTS: We observed substantial heterogeneity of results and interpretations among the 4 methods. Complete agreement among methods with respect to LDL subclass phenotyping occurred in only 8% (n = 3) of the persons studied. NMR and GGE agreed most frequently at 70% (n = 28), whereas VAP matched least often. CONCLUSIONS: As measurement of LDL subclasses becomes increasingly important, standardization of methods is needed. Variation among currently available methods renders them unreliable and limits their clinical usefulness.

Negative mood endures after completion of high-altitude military training.

BACKGROUND: Associations between physical and emotional stress and negative mood states have been documented in a variety of populations. In military personnel, more physical symptoms and decrements in ability to perform critical tasks have been shown to accompany such stress-induced negative mood. Most research in this area has focused on immediate effects of stress on mood. PURPOSE: We wondered what immediate mood effects strenuous training would have on Marines, what mood effects would endure 30 and 90 days after completion of training, and how mood scores would compare with normative data. METHODS: Sixty male Marines (M age = 19 years, range = 18-28) completed the Profile of Mood States (POMS) at multiple time points before and after participating in a 30-day, cold weather, high-altitude field training exercise. Anthropometric measurements were taken at the same time points. RESULTS: The Marines reported significant increases in POMS scores from baseline to completion of training, most of which endured up to 90 days. The anger and fatigue scores reported by the Marines were comparable to adult male psychiatric outpatient norms. CONCLUSIONS: Rigorous training in challenging environments may result in enduring negative moods that approach levels of clinical significance and may have implications for readiness for duty and performance of critical tasks. Behavioral medicine interventions may be helpful in military populations to reduce the impact of negative mood.

Exercise improves plasma lipid profiles and modifies lipoprotein composition in guinea pigs.

These studies were conducted to determine the effects of exercise training on plasma lipoprotein levels and metabolism in the guinea pig to evaluate potential utilization of this model for studies of exercise-mediated effects on the regulation of sterol and lipoprotein metabolism and atherosclerosis regression. Male guinea pigs (n = 5 per group) were randomly assigned to either a control or an exercise group. The exercise protocol consisted of a 7-week training program, 5 days/wk on a rodent treadmill. Final speed and duration were 33 meters/min for 30-40 min per session. Guinea pigs in the exercise group had 33% lower plasma triacylglycerol concentrations (P < 0.01), 66% higher HDL cholesterol levels (P < 0.05) and 31% lower plasma free fatty acids (P < 0.05) than guinea pigs from the non-exercised group. In addition, lipoprotein lipase activity in the heart was 50% higher (P < 0.025) in guinea pigs allocated to the exercise protocol. Exercise training resulted in modifications in composition and size of lipoproteins. The concentrations of free cholesterol in LDL and HDL were higher in the exercised guinea pigs. The LDL peak density values were lower in guinea pigs from the exercise group compared to controls suggesting that exercise training resulted in larger LDL particles. In contrast, no significant effects due to exercise were observed in hepatic cholesterol concentrations, hepatic HMG-CoA reductase activity or LDL binding to guinea pig hepatic membranes. These data indicate that exercise had a more pronounced effect on the intravascular processing of lipoproteins than on hepatic cholesterol metabolism. In addition, the pattern of changes in guinea pig lipoprotein metabolism, in response to exercise training, was similar to reported effects in humans.