Body temperature modulates the antioxidant and acute immune responses to exercise

Abstract

The aim of this study was to determine the effects of whole body heat in combination with exercise on the oxidative stress and acute phase immune response. Nine male endurance-trained athletes voluntarily performed two running bouts of 45 minutes at 75–80% of VO_2max in a climatic chamber in two conditions: cold and hot humid environment. Leukocyte, neutrophil and basophil counts significantly rose after exercise in both environments; it was significantly greater in the hot environment. Lymphocyte and neutrophil antioxidant enzyme activities and carbonyl index significantly increased or decreased after exercise only in the hot environment, respectively. The lymphocytes expression of catalase, Hsp72 and CuZn-superoxide dismutase was increased in the hot environment and Sirt3 in the cold environment, mainly during recovery. In conclusion, the increased core body temperature results in the acute phase immune response associated to intense exercise and in the immune cell adaptations to counteract the oxidative stress situation.     

Oxidative stress and antioxidant defense responses of Etroplus suratensis to acute temperature fluctuations

Fishes are always exposed to various environmental stresses and the chances of succumbing to such stresses are of great physiological concern. Any change in temperature from the ambient condition can induce various metabolic and physiological changes in the body. The present study evaluates the effects of temperature induced stress on the antioxidant profile of Etroplus suratensis such as superoxide dismutase, catalase, glutathione peroxidase and lipid peroxidation. Fishes of same size were kept in a thermostatized bath at three different temperature regimes viz 16 °C, 27 °C (ambient temperature) and 38 °C for 72 h. These temperatures were selected based on the CT Max (Critical Thermal Maximum) and CT Min (Critical Thermal Minimum) exhibited by E. suratensis. Superoxide dismutase and catalase activity was found maximum in brain and muscle respectively during the 48th hour of exposure in fishes kept at 38 °C. At 16 °C the antioxidant response of glutathione peroxidase was maximum in muscles, whereas the lipid peroxidation rate was found to be high in gills compared to other tissues. The profound increase in the levels of oxidative stress related biomarkers indicate that the thermal stressors severely affected oxidative state of E. suratensis by the second day of experiment. Such down-regulation of redox state accompanied with the induction of oxidative stress cascade may lead to physiological damage in various tissues in fishes, in vivo. However current data indicate that a transition to low and high temperature environment from ambient condition severely affected the levels and profile of the antioxidant markers overtime in E. suratensis.     

Body temperature related factors diminishing the drive to exercise

The effects of slightly below-normal body temperatures (delta Tcore-0.5 to 1 degree C) on exercise performance were examined in four series of studies employing a standardized precooling maneuver. In both the precooling tests and the control tests the subjects exercised on a cycle ergometer at an ambient temperature of 18 degrees C with the following results. In series 1, the subjects were exercising at a heart rate of 120 beats X min-1. Work rate and oxygen pulse were significantly increased, and sweat rate was less elevated in precooling tests than in controls. In series 2, in 12 well-trained rowers subjected to an incremental performance test, maximum work rate, peak VO2, time to exhaustion, and total work were not reduced in precooling tests. Eight well-trained rowers in series 3 were requested to work as hard as possible for 1 h. The mean work rate, VO2, and oxygen pulse were increased in the precooling tests by 6.8, 9.6, and 5.6%, respectively, whereas the sweat rate was 20% lower. In series 4 after a 16-min period of easy exercise (phase 1) the subjects exercised at a work rate corresponding to 80% VO2max up to exhaustion. Endurance time at this work rate was increased in precooling tests by 12% (18.5 vs. 20.8 min, p = 0.035). Heart rate was lower throughout the exercise period in precooling tests.(ABSTRACT TRUNCATED AT 250 WORDS)     

Indomethacin modulates circulating cytokine responses to strenuous exercise in humans

Physical stress is associated with circulating cytokinemia. However the mechanisms of cytokine regulation during such stress are not clearly defined. Non-steroidal anti-inflammatory drugs (NSAIDs), including indomethacin, are widely used in countering the effects of excessive exercise, but their impact on circulating pro- and anti-inflammatory cytokine production in healthy humans also remains unclear. This study investigated the effect of five days of oral indomethacin treatment (75 mg per day) on the serum concentrations of IL-6, IL-10, IL-12, and TNF-alpha induced by exercising healthy volunteers. The results demonstrate that indomethacin does not alter resting serum cytokine concentrations. Increased circulating levels were noted, however, for all four cytokines with exercise, but with a different time-course. During and after strenuous physical exercise, indomethacin treatment blunted serum IL-6, and augmented TNF-alpha and IL-10. These findings may have important implications for both host defense and the injuries associated with excessively vigorous exercise.     

Chitin modulates innate immune responses of keratinocytes

Background

Chitin, after cellulose the second most abundant polysaccharide in nature, is an essential component of exoskeletons of crabs, shrimps and insects and protects these organisms from harsh conditions in their environment. Unexpectedly, chitin has been found to activate innate immune cells and to elicit murine airway inflammation. The skin represents the outer barrier of the human host defense and is in frequent contact with chitin-bearing organisms, such as house-dust mites or flies. The effects of chitin on keratinocytes, however, are poorly understood.

Methodology/Principal Findings

We hypothesized that chitin stimulates keratinocytes and thereby modulates the innate immune response of the skin. Here we show that chitin is bioactive on primary and immortalized keratinocytes by triggering production of pro-inflammatory cytokines and chemokines. Chitin stimulation further induced the expression of the Toll-like receptor (TLR) TLR4 on keratinocytes at mRNA and protein level. Chitin-induced effects were mainly abrogated when TLR2 was blocked, suggesting that TLR2 senses chitin on keratinocytes.

Conclusions/Significance

We speculate that chitin-bearing organisms modulate the innate immune response towards pathogens by upregulating secretion of cytokines and chemokines and expression of MyD88-associated TLRs, two major components of innate immunity. The clinical relevance of this mechanism remains to be defined.     

Lymphocyte enzymatic antioxidant responses to oxidative stress following high-intensity interval exercise

The purposes of this study were to 1) examine the immune and oxidative stress responses following high-intensity interval training (HIIT); 2) determine changes in antioxidant enzyme gene expression and enzyme activity in lymphocytes following HIIT; and 3) assess pre-HIIT, 3-h post-HIIT, and 24-h post-HIIT lymphocyte cell viability following hydrogen peroxide exposure in vitro. Eight recreationally active males completed three identical HIIT protocols. Blood samples were obtained at preexercise, immediately postexercise, 3 h postexercise, and 24 h postexercise. Total number of circulating leukocytes, lymphocytes, and neutrophils, as well as lymphocyte antioxidant enzyme activities, gene expression, cell viability (CV), and plasma thiobarbituric acid-reactive substance (TBARS) levels, were measured. Analytes were compared using a three (day) × four (time) ANOVA with repeated measures on both day and time. The a priori significance level for all analyses was P < 0.05. Significant increases in superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities were observed in lymphocytes following HIIT. No significant increases in lymphocyte SOD, CAT, or GPX gene expression were found. A significant increase in TBARS was found immediately post-HIIT on days 1 and 2. Lymphocyte CV in vitro significantly increased on days 2 and 3 compared with day 1. Additionally, there was a significant decrease in CV at 3 h compared with pre- and 24 h postexercise. These findings indicate lymphocytes respond to oxidative stress by increasing antioxidant enzyme activity. Additionally, HIIT causes oxidative stress but did not induce a significant postexercise lymphocytopenia. Analyses in vitro suggest that lymphocytes may become more resistant to subsequent episodes of oxidative stress. Furthermore, the analysis in vitro confirms that lymphocytes are more vulnerable to cytotoxic molecules during recovery from exercise.     

Metabolic and endocrine responses to graded exercise under acute hypoxia

Eight male subjects (24 +/- 1 years old) performed graded ergocycle exercises in normoxic (N) and acute hypoxic (H) conditions (14.5% O2). VO2max decreased from 55.5 +/- 1.3 to 45.8 +/- 1.4 ml . kg-1 . min-1 in H condition. Plasma glucose and free fatty acid concentrations remained unchanged throughout exercise in both conditions. Increase in blood lactate concentration was associated with relative workload in both conditions. At VO2max lactate concentrations were similar in the two conditions, plasma insulin, glucagon, and LH concentrations did not significantly change in either. Plasma delta 4-androstenedione and testosterone increased in a similar manner in both conditions. Finally plasma norepinephrine concentration reached at VO2max was significantly lower in hypoxia. These results suggest that acute moderate hypoxia does not affect metabolic and hormonal responses to short exercise performed at similar relative workloads, i.e. when the reduction of VO2max due to hypoxia is taken into consideration. The lower catecholamine response to maximal exercise under acute hypoxia might suggest that the sympathetic response could be related to relative as well as absolute workloads.     

Metabolic and temperature responses to physical exercise in thyroidectomized dogs.

The purpose of the present work was to further elucidate the role of thyroid hormones in the control of body temperature and metabolism during physical exercise. Changes in rectal temperature (Tre), some parameters of exercise-metabolism and in the plasma noradrenaline (NA) levels were examined in eight dogs performing submaximal treadmill exercise to exhaustion before and after thyroidectomy (THY). The metabolic 'responses to adrenaline (A) infusion were also compared in intact and THY dogs. During the exercise performed by THY dogs Tre increases were markedly attenuated, plasma FFA level increases were reduced and the pattern of plasma NA changes was modified in comparison with control runs. The reduced exercise-induced FFA mobilization in THY dogs might be attributed to a lower activation of the adrenergic system in the later stage of exercise and to the weaker lipolytic action of catecholamines. The attenuated Tre increases during exercise performed by THY dogs and the exercise-hyperthermia described previously in dogs treated with thyroid ormones suggest that an optimum level of thyroid hormones is necessary to induce typical changes in body temperature during physical exercise.     

Body temperature responses of Savanna Brown goat to the harmattan and hot-dry season

Rectal and vaginal temperature responses of the Savanna Brown goat indigenous to the Nigerian guinea savanna were determined during the harmattan and the hot-dry season. Measurements were made at 06:00h and at 14:00h after 8h exposure to field conditions. At the 06:00h measurements during the harmattan, all animals were observed to shiver. A significant (P<0.01) positive correlation was found between rectal (T_re) and vaginal temperatures. During the harmattan, mean T_re was 38.2C at 06:00h and 39.7C at 14:00h; the mean difference, T_re was 1.5C. During the hot-dry season, T_re at 06:00h was 38.1C, and at 14:00h, 38.7; T_re was 0.6C. It is concluded that the harmattan is thermally more stressful than the hot-dry season and that passive thermolability may not be an important mechanism in the Savanna Brown goat in adaptation to thermal stress.     

Dopamine modulates acute responses to cocaine, nicotine and ethanol in Drosophila

BACKGROUND: Drugs of abuse have a common property in mammals, which is their ability to facilitate the release of the neurotransmitter and neuromodulator dopamine in specific brain regions involved in reward and motivation. This increase in synaptic dopamine levels is believed to act as a positive reinforcer and to mediate some of the acute responses to drugs. The mechanisms by which dopamine regulates acute drug responses and addiction remain unknown. RESULTS: We present evidence that dopamine plays a role in the responses of Drosophila to cocaine, nicotine or ethanol. We used a startle-induced negative geotaxis assay and a locomotor tracking system to measure the effect of psychostimulants on fly behavior. Using these assays, we show that acute responses to cocaine and nicotine are blunted by pharmacologically induced reductions in dopamine levels. Cocaine and nicotine showed a high degree of synergy in their effects, which is consistent with an action through convergent pathways. In addition, we found that dopamine is involved in the acute locomotor-activating effect, but not the sedating effect, of ethanol. CONCLUSIONS: We show that in Drosophila, as in mammals, dopaminergic pathways play a role in modulating specific behavioral responses to cocaine, nicotine or ethanol. We therefore suggest that Drosophila can be used as a genetically tractable model system in which to study the mechanisms underlying behavioral responses to multiple drugs of abuse.     

Brain heterogeneity leads to differential innate immune responses and modulates pathogenesis of viral infections

The central nervous system (CNS) is a highly complex organ with highly specialized cell subtypes. Viral infections often target specific structures of the brain and replicate in certain regions. Studies in mice deficient in type I Interferon (IFN) receptor or IFN-β have highlighted the importance of the type I IFN system against viral infections and non-viral autoimmune disorders in the CNS. Direct antiviral effects of type I IFNs appear to be crucial in limiting early spread of a number of viruses in CNS tissues. Increased efforts have been made to characterize IFN expression and responses in the brain. In this context, it is important to identify cells that produce IFN, decipher pathways leading to type I IFN expression and to characterize responding cells. In this review we give an overview about region specific aspects that influence local innate immune responses. The route of entry is critical, but also the susceptibility of different cell types, heterogeneity in subpopulations and micro-environmental cues play an important role in antiviral responses.Recent work has outlined the tremendous importance of type I IFNs, particularly in the limitation of viral spread within the CNS. This review will address recent advances in understanding the mechanisms of local type I IFN production and response, in the particular context of the CNS.     

Escherichia coli heme oxygenase modulates host innate immune responses

Induction of mammalian heme oxygenase (HO)‐1 and exposure of animals to carbon monoxide (CO) ameliorates experimental colitis. When enteric bacteria, including Escherichia coli, are exposed to low iron conditions, they express an HO‐like enzyme, chuS, and metabolize heme into iron, biliverdin and CO. Given the abundance of enteric bacteria residing in the intestinal lumen, our postulate was that commensal intestinal bacteria may be a significant source of CO and those that express chuS and other Ho‐like molecules suppress inflammatory immune responses through release of CO. According to real‐time PCR, exposure of mice to CO results in changes in enteric bacterial composition and increases E. coli 16S and chuS DNA. Moreover, the severity of experimental colitis correlates positively with E. coli chuS expression in IL‐10 deficient mice. To explore functional roles, E. coli were genetically modified to overexpress chuS or the chuS gene was deleted. Co‐culture of chuS‐overexpressing E. coli with bone marrow‐derived macrophages resulted in less IL‐12p40 and greater IL‐10 secretion than in wild‐type or chuS‐deficient E. coli. Mice infected with chuS‐overexpressing E. coli have more hepatic CO and less serum IL‐12 p40 than mice infected with chuS‐deficient E. coli. Thus, CO alters the composition of the commensal intestinal microbiota and expands populations of E. coli that harbor the chuS gene. These bacteria are capable of attenuating innate immune responses through expression of chuS. Bacterial HO‐like molecules and bacteria‐derived CO may represent novel targets for therapeutic intervention in inflammatory conditions.     

Glucose administration before exercise modulates catecholaminergic responses in glycogen-depleted subjects

Gozal, David, Patrice Thiriet, Jean Marie Cottet-Emard,Dieudonné Wouassi, Emmanuel Bitanga, André Geyssant, JeanMarc Pequignot, and Marcel Sagnol. Glucose administration before exercise modulates catecholaminergic responses in glycogen-depleted subjects. J. Appl. Physiol. 82(1):248-256, 1997.In glycogen-depleted subjects (GD) a nonlinearincrease in epinephrine (Epi) and norepinephrine (NE) parallels bloodlactate (La) during graded exercise. The effect of glucose(Glc) supplementation and route of administration on theserelationships was studied in 26 GD athletes who were randomly assignedto receive 1.3 g/kg Glc by slow intravenous infusion (IV;n = 9), oral administration (PO;n = 9), or artificially sweetenedplacebo in 1 liter of water (Asp; n = 8) in the 2 h preceding a graded maximal exercise. Performance and Lawere similar among the three groups in normal glycogen (NG) or GDconditions. However, slightly improved performances were observed in GDcompared with NG and were associated with a shift to the right in Lacurves. Blood Glc concentrations were higher in IV and PO beforeexercise, but they rapidly decreased to lowest levels in IV, graduallydecreased over time in PO, and remained stable in Asp or NG. Insulinconcentrations were highest in IV and lowest in Asp and NG at onset ofexercise, rapidly decreasing in IV and PO although remaining at higherlevels than in Asp or NG. In contrast, higher serum levels of freefatty acids were measured during exercise in Asp with no significant differences in glucagon or glycerol among the three groups. Free andsulfated NE increases were smaller in IV than in PO and Asp onexhaustion. In contrast, free and conjugated Epi were most increased inIV, with smallest increases in Asp. Dopamine levels were most increasedin IV at exhaustion. We conclude that the changes of Epi and NEconcentrations, associated with the activation of glucoregulatorymechanisms, including hyperinsulinemia, display different magnitude andtime courses during exercise in GD subjects who receive oral vs.intravenous load of Glc before exercise. We speculate that themagnitude of insulin surge after acutely increased Glc before exercisein GD subjects may exert dissociative effects on adrenal-dependentglycogenolysis and on sympathetic responses.

     

Cytokine responses to acute and chronic exercise in multiple sclerosis.

Regular exercise reduces functional loss associated with multiple sclerosis (MS). However, the impact of exercise on inflammatory mediators associated with disease activity remains relatively unexplored. The purpose of this study was to determine whether ambulatory MS subjects would respond similarly to aerobic cycle training compared with matched controls on circulating immune variables, interleukin (IL)-6, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma. Eleven MS and 11 non-MS control subjects (8 women and 3 men in both groups) matched in age, height, body mass, body fat, and peak O(2) uptake completed the study. Subjects completed 30 min of cycle ergometry at 60% of peak O(2) uptake, 3 day/wk for 8 wk. Plasma cytokine concentrations were determined before and after exercise at weeks 0, 4, and 8. MS and control subjects showed a similar cytokine responses to exercise. IL-6 at rest tended to decrease (P = 0.08) with training in both groups. Resting plasma TNF-alpha tended to be higher in MS compared with controls throughout the study (P = 0.08). MS subjects showed elevated resting TNF-alpha in MS at the end of the 8-wk program (P = 0.04), whereas resting TNF-alpha remained unchanged in controls (P > 0.05). Resting plasma IFN-gamma at rest was elevated in MS subjects (P = 0.008) and unchanged in controls at the end of the intervention (P > 0.05). The response of plasma IL-6, TNF-alpha, and IFN-gamma after a single bout of exercise was similar between MS and control subjects (P > 0.05). Additional research to understand the impact of exercise on immune variables in MS is warranted.     

Acute phase immune response to exercise coexists with decreased neutrophil antioxidant enzyme defences

Long-duration or damaging exercise initiates reactions that resemble the acute phase response to infection and induces neutrophil priming for oxidative activity. Our objective was to establish the status of the antioxidant defences and of the oxidative equilibrium in the neutrophils of sportsmen prior to and after intense physical exercise. Nine voluntary male professional cyclists participated in this study. The exercise was a cycling mountain stage (171 km) and the cyclists took a mean ±SEM of 270 ±12 min to complete it. We determined the activities of catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), the levels and activity of superoxide dismutase (SOD), the concentrations of ascorbate, glutathione and glutathione disulphide (GSSG) and DNA levels in neutrophils. The cycling stage decreased enzyme activities expressed per DNA units: CAT (33%), SOD (38%), GPx (65%); increased ascorbate concentration in neutrophils and decreased the GSH/GSSG ratio and the enzyme activities expressed per DNA units. Neutrophils could contribute to plasma antioxidant defences against oxidative stress induced by exercise because they probably provide antioxidant enzymes and ascorbate.     

Immunocalins: a lipocalin subfamily that modulates immune and inflammatory responses

A subset of the lipocalins, notably alpha(1)-acid glycoprotein, alpha(1)-microglobulin, and glycodelin, exert significant immunomodulatory effects in vitro. Interestingly, all three are encoded from the q32-34 region of human chromosome 9, together with at least four other lipocalins (neutrophil gelatinase-associated lipocalin, complement factor gamma-subunit, tear prealbumin, and prostaglandin D synthase) that also may have anti-inflammatory and/or antimicrobial activity. This review addresses important features of this genetically linked subfamily of lipocalins (involvement with the acute phase response, immunomodulatory and anti-inflammatory properties, the tissue localization, complex formation with other proteins and receptors, etc.). It is likely that these proteins have evolved to be an integrated part of the body's defense system as part of the extended cytokine network. Its members exert a regulatory, dampening influence on the inflammatory cascade, thereby protecting against tissue damage from excessive inflammation. That most major mammalian allergens are lipocalins may reflect this connection of lipocalins with the immune system. We propose that this immunologically active lipocalin subset be named the 'immunocalins', signifying not only the structural homology and close genetic linkage of its members, but also their protective involvement with immunological and inflammatory processes. As immune mediators, immunocalins appear to use at least three interactive sites: the lipocalin 'pocket', binding sites for other plasma proteins, and binding sites for cell surface receptors.