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      Effects of Combined Stress during Intense Training on Cellular Immunity, Hormones and Respiratory Infections

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          Abstract

          Objectives: This study was designed to determine immune and hormonal changes and their relationship with the incidence of upper respiratory tract infections (URTIs) during an extremely stressful military training (3 weeks of physical conditioning followed by a 5-day combat course with energy restriction, sleep deprivation and psychological stress). Methods: Blood samples were collected from 21 cadets (21 ± 2 years old) before training and after the combat course for analysis of leukocyte and lymphocyte subpopulations, serum cytokines [interleukin-6 (IL-6), IL-1β and IL-10], and hormones [catecholamines, cortisol, leptin, total insulin-like growth factor I (IGF-I), prolactin, dehydroepiandrosterone sulfate (DHEAS) and testosterone]. Symptoms of URTI were recorded from health logs and medical examinations during training. Results: After the combat course, total leukocyte and neutrophil counts were significantly increased while total lymphocytes were unchanged. In lymphocyte subsets, NK cells were reduced (p < 0.01), while CD4+ and CD19+ (B) cells were increased. Levels of IL-6 were increased (p < 0.01), while those of IL-1β and IL-10 were unchanged. Norepinephrine and dopamine levels were increased, while those of cortisol were reduced. Levels of leptin, testosterone, prolactin and total IGF-I were reduced, while those of DHEAS were increased. The incidence of URTI increased during the training (χ<sup>2</sup> = 53.48, p < 0.05). After training data analysis showed a significant correlation between URTIs and NK cells (p = 0.0023). Training-induced changes in immune and hormonal parameters were correlated. Conclusions: Blood NK cell levels are related to increased respiratory infections during physical training in a multistressor environment. The training-induced decreases in immunostimulatory hormone levels may have triggered immunosuppression.

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          Most cited references 19

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          Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression.

          Nutritional deprivation suppresses immune function. The cloning of the obese gene and identification of its protein product leptin has provided fundamental insight into the hypothalamic regulation of body weight. Circulating levels of this adipocyte-derived hormone are proportional to fat mass but maybe lowered rapidly by fasting or increased by inflammatory mediators. The impaired T-cell immunity of mice now known to be defective in leptin (ob/ob) or its receptor (db/db), has never been explained. Impaired cell-mediated immunity and reduced levels of leptin are both features of low body weight in humans. Indeed, malnutrition predisposes to death from infectious diseases. We report here that leptin has a specific effect on T-lymphocyte responses, differentially regulating the proliferation of naive and memory T cells. Leptin increased Th1 and suppressed Th2 cytokine production. Administration of leptin to mice reversed the immunosuppressive effects of acute starvation. Our findings suggest a new role for leptin in linking nutritional status to cognate cellular immune function, and provide a molecular mechanism to account for the immune dysfunction observed in starvation.
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            Interleukin-6 production in contracting human skeletal muscle is influenced by pre-exercise muscle glycogen content.

            1. Prolonged exercise results in a progressive decline in glycogen content and a concomitant increase in the release of the cytokine interleukin-6 (IL-6) from contracting muscle. This study tests the hypothesis that the exercise-induced IL-6 release from contracting muscle is linked to the intramuscular glycogen availability. 2. Seven men performed 5 h of a two-legged knee-extensor exercise, with one leg with normal, and one leg with reduced, muscle glycogen content. Muscle biopsies were obtained before (pre-ex), immediately after (end-ex) and 3 h into recovery (3 h rec) from exercise in both legs. In addition, catheters were placed in one femoral artery and both femoral veins and blood was sampled from these catheters prior to exercise and at 1 h intervals during exercise and into recovery. 3. Pre-exercise glycogen content was lower in the glycogen-depleted leg compared with the control leg. Intramuscular IL-6 mRNA levels increased with exercise in both legs, but this increase was augmented in the leg having the lowest glycogen content at end-ex. The arterial plasma concentration of IL-6 increased from 0.6 +/- 0.1 ng x l(-1) pre-ex to 21.7 +/- 5.6 ng x l(-1) end-ex. The depleted leg had already released IL-6 after 1 h (4.38 +/- 2.80 ng x min(-1) (P < 0.05)), whereas no significant release was observed in the control leg (0.36 +/- 0.14 ng x min(-1)). A significant net IL-6 release was not observed until 2 h in the control leg. 4. This study demonstrates that glycogen availability is associated with alterations in the rate of IL-6 production and release in contracting skeletal muscle.
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              The effects of moderate exercise training on natural killer cells and acute upper respiratory tract infections.

              A randomly controlled 15-wk exercise training (ET) study (five 45-min sessions/wk, brisk walking at 60% heart rate reserve) with a group of 36 mildly obese, sedentary women was conducted to investigate the relationship between improvement in cardiorespiratory fitness, changes in natural killer (NK) cell number and activity, and acute upper respiratory tract infection (URI) symptomatology. The study was conducted using a 2 (exercise and nonexercise groups) x 3 (baseline, 6-, and 15-wk testing sessions) factorial design, with data analyzed using repeated measures ANOVA. No significant change in NK cell number occurred as a result of ET as measured by the CD16 and Leu-19 monoclonal antibodies. ET did have a significant effect on NK cell activity (E:T 50:1) especially during the initial 6-wk period [F(2.68) = 12.34, p less than 0.001]. Using data from daily logs kept by each subject, the exercise group was found to have significantly fewer URI symptom days/incident than the nonexercise group (3.6 +/- 0.7 vs 7.0 +/- 1.4 days, respectively, p = 0.049). Improvement in cardiorespiratory fitness was correlated significantly with a reduction in URI symptom days/incident (r = 0.37, p = 0.025) and a change in NK cell activity from baseline to six but not 15 wks (r = 0.35, p = 0.036). In summary, moderate ET is associated with elevated NK cell activity after six but not 15 weeks, and reduced URI symptomatology in comparison to a randomized, sedentary control group.
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                Author and article information

                Journal
                NIM
                Neuroimmunomodulation
                10.1159/issn.1021-7401
                Neuroimmunomodulation
                S. Karger AG
                1021-7401
                1423-0216
                2005
                May 2005
                17 May 2005
                : 12
                : 3
                : 164-172
                Affiliations
                aDepartment of Physiology, IMASSA, Brétigny-sur-Orge, and bDepartment of Radiobiology and Radiopathology, CRSSA, Grenoble, France
                Article
                84849 Neuroimmunomodulation 2005;12:164–172
                10.1159/000084849
                15905625
                © 2005 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 2, Tables: 3, References: 33, Pages: 9
                Categories
                Original Paper

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