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Experimental study on neuroendocrinological and immunological characteristics of the military-trained artillerymen

LI, Xin; HUANG, Wen-xu; LU, Ju-ming; YANG, Guang; MA, Fang-ling; LAN, Ya-ting; MENG, Jun-hua; DOU, Jing-tao

doi: 10.3760/cma.j.issn.0366-6999.2012.07.019
Original article
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Background Over one million soldiers were treated for battle- or training-fatigue during World War II. Of all ground combat troops, 37% were discharged for psychiatric reasons due to fatigue. The neuroendocrinological and immunological systems played important roles in the work-related fatigue of military personnel. The aim of this study was to investigate the characteristics of fatigue associated with military operations, and we observed changes in the regulatory functions of the neuroendocrinological and immunological systems that may provide theoretical support for improving the combat effectiveness of armies.

Methods A total of 240 soldiers from the Field Artillery regiment were selected as subjects. Researchers and subjects received training before participating in the study. Data of the subjects’ medical histories, physical examinations, scores on a fatigue assessment scale, and assessments of pituitary-adrenal hormones (adrenal cortical hormone (ACTH), cortical hormone (F), and 24-hour urine-free cortisol (UFC)), pituitary-gonadal hormones (luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, estradiol (E2), and prolactin (PRL)), pituitary-thyroid hormones (thyroid-stimulating hormone (TSH), thyroxine (TT4), triiodothyronine (TT3), free thyroxine (FT4), and free triiodothyronine (FT3)), and cellular immune parameters (CD3+, CD4+, CD8+, CD4+/CD8+, B, and NK cells) were investigated before and after large-scale and high-intensity field exercises. Data were statistically analyzed with Student’s t test using SPSS software (version 13.0), and P values <0.05 were deemed to be significant.

Results After the high-intensity military training, the scores on the fatigue scale reflected significant increases of feeling of unpleasantness among soldiers. Additionally, the symptom checklist showed notable increases in somatization scores and significant decreases in psychoticism scores. After intensive military work, levels of plasma ACTH, F, and UFC of soldiers were decreased (P <0.01). The level of testosterone decreased significantly after the maneuver ((23.51±6.49) versus (18.89±5.89) nmol/L; P <0.001), whereas the thyroid function (TT3, FT4, and FT3) was markedly increased after the maneuver (P <0.01). The number of CD3+, CD4+, CD4+/CD8+ cells, and B lymphocytes were decreased (P <0.05), and NK cells were increased (P <0.001) after the maneuver.

Conclusions Following high-intensity military operations, the psychological tolerance of soldiers was depressed. And the hypoadrenocorticism (the functional decreases of hypothalamic-pituitary-gonadal and abnormal pituitary-thyroid axis) contributed to the increased levels of fatigue. Hypoimmunity may increase the susceptibility to diseases after high-intensity military operations.

Department of Endocrinology (Li X, Lu JM, Yang G, Ma FL, Meng JH and Dou JT), Department of Clinical Laboratory (Lan YT), Chinese People’s Liberation Army General Hospital, Beijing 100853, China Artillery Regiment of 66116 People’s Liberation Army Troops, China (Huang WX)

Correspondence to: Prof. LU Ju-ming, Department of Endocrinology, Chinese People’s Liberation Army General Hospital, Beijing 100853, China (Tel: 86-10-55499096. Fax: 86-10-55499391.

Email: lujuming301@126.com)

This work was supported by a grant from the Military Medicine Research Program of General Logistics Department (No. 08G136).

(Received August 15, 2011)

Edited by GUO Li-shao

Combat conditions or numerous intensive and long military training courses can result in excessive physiological stress or drain the energy and physical ability of soldiers in a short time.1,2 Thus, modern soldiers are likely to suffer from work-related fatigue, which can severely affect the effectiveness of an army in combat situations. Extensive and in-depth researches have been conducted in various countries to clarify the pathogenesis of military work-related fatigue and to effectively prevent and treat this condition to maximize the combat effectiveness of armies. In our opinion, the neuroendocri-nological and immunological systems play important roles in the work-related fatigue of military personnel.

This research focused on the soldiers in a field army to assess the changes of fatigue levels; functions of the pituitary-adrenal, pituitary-gonadal, and pituitary-thyroid axes; cellular immunity indices; scores on work-related fatigue scales; and self-ratings of psychohygiene (SCL-90) before and after large-scale intensive military maneuvers to provide a theoretical support for improving the combat effectiveness of soldiers in such military operations.

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METHODS

Subjects

The sample consisted of 240 field artillery soldiers and all of them were healthy men aged 18-24 (20.11±2.24) years.

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Training methods

Medical histories were obtained, physical examinations were performed, self-rated psychohygiene (SCL-90) and work-related fatigue scales were completed, and blood and urine samples were collected before the military operation. These measures were repeated after a 7-day large-scale military maneuver involving artillery.

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Test indices

Test indices included data of height, weight, blood pressure, pulse rate, pituitary-adrenal axis (including levels of plasma adrenal cortical hormone (ACTH), cortical hormone (F), and 24-hour urine-free cortisol (UFC)), pituitary-gonadal axis (including levels of luteinizing hormone (LH), testosterone, and estradiol (E2)), pituitary-thyroid axis (including levels of thyroid-stimulating hormone (TSH), thyroxine (TT4), tri-iodothyronine (TT3), free thyroxine (FT4), and free tri-iodothyronine (FT3)), cellular immunity indices (CD3+, CD4+, CD8+, CD4+/CD8+, B, and NK), work-related fatigue scales, and self-rated psychohygiene (SCL-90).

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Samples collection

Samples were collected and scales were completed before and after large-scale military maneuvers involving artillery.

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Immunological tests

Fasting venous whole blood was taken in a 100-μl aliquot. We then added 10 μl of antibody solution, which was followed by 500 μl of hemolysin after incubation at room temperature for 20 minutes. The mixture was maintained at room temperature for an additional 10 minutes, and then 500 μl of sheath fluid was added. After incubation for 10 minutes at room temperature, T, B, and NK lymphocyte subsets (including CD3+, CD4+, CD8+, CD4+/CD8+, B, and NK cells) were assessed with a blood detector.

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The 24-hour urine collection

Twenty-four-hour urine samples were collected after drinking normal volumes of fluids under medical supervision.

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Symptom checklist

The symptom checklist 90 (SCL-90) contains 90 items in nine subscales that are rated between 1 and 4 and higher scores indicate worse states of psychological health.

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Assaying methods

Blood samples for detecting hormones were collected in the morning after at least 8 hour of fasting overnight. Plasma ACTH, F, and 24-hour urine-free cortisol were detected with radio immunoassay (IMMULITE 2000); pituitary-gonadal hormones and thyroid hormones were detected with Chemiluminescence (Centaur Automated Chemiluminescence Systems, Siemens, Germany).

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Statistical analyses

Test results were reported as means and standard deviations. Statistical analyses were conducted using SPSS software (version 13.0, SPSS Inc., USA). Comparisons of data obtained before and after the military operations were performed with Student’s paired t test. P values <0.05 were deemed to indicate statistically significant differences.

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RESULTS

Comparison of the general status before and after the maneuver

Comparison of the general status of the soldiers before and after the maneuvers showed increased heart rates ((68.88±7.68) versus (75.69±8.50) beats/min; P <0.05) after the maneuvers, but no other significant differences with respect to other factors (e.g., height, weight, systolic pressure, and diastolic pressure) were seen (Table 1). Functional comparison of adrenal status before and after the maneuver Levels of ACTH ((6.58±3.54) versus (6.11±3.37) pmol/L; P <0.05), F ((336.97±105.23) versus (283.94±84.61) nmol/L; P <0.001), and UFC ((426.39±162.35) versus (371.76±155.51) nmol/24 hour; P <0.001) decreased, indicating that the functional status of the adrenal cortex was weakened after the 7-day intensive maneuver (Table 2). Functional comparison of the gonadal status before and after the maneuver The level of testosterone declined after the maneuver ((23.51±6.49) versus (18.89±5.89) nmol/L; P <0.001), but we found no significant differences between the levels of LH or E2 before and after the maneuver (P >0.05; Table 3).

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Functional comparison of the thyroid status before and after the maneuver

Comparison of the thyroid functional status of the soldiers before and after the maneuver revealed the following variables: TT3 ((2.13±0.30) versus (2.72±2.26) nmol/L, P <0.05), FT4 ((13.45±1.45) versus (15.92±1.95) pmol/L, P <0.001), FT3 ((5.23±0.42) versus (5.61±0.58) pmol/L, P <0.001), and TSH ((2.94±1.46) versus (2.47±1.36) mU/L, P <0.001). However, no significant change was found with respect to TT4. These results indicated that the thyroid function of the soldiers was markedly increased after the maneuver, which is consistent with their increased heart rates (Table 4).

Table 1

Table 1

Table 2

Table 2

Table 3

Table 3

Table 4

Table 4

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Comparison of the immunological function before and after the maneuver

The immunological function showed marked weakening after the maneuver as indicated by decreased numbers of CD3+ cells (0.58±0.10 versus 0.57±0.10, P <0.001), CD4+ cells (0.29±0.05 versus 0.26±0.06, P <0.001), CD4+/CD8+ cells (1.18±0.43 versus 1.02±0.42, P <0.001), and B lymphocytes (0.13±0.04 versus 0.11±0.04, P <0.001), and by an increased level of NK cells (0.24±0.09 versus 0.30±0.11, P <0.001).

Given that B cell differentiation is inhibited by NK cells, a reduced number of B cells plus an increased number of NK cells would be expected to lead to inhibition of the proliferation and differentiation of B cells and antibody responses (Table 5).

Table 5

Table 5

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Comparison of fatigue scale scores before and after the maneuver

The results showed that unpleasant feelings were significantly increased after the maneuver (from 7.53±2.64 to 8.02±3.06, P <0.05). However, we found no significant differences in the feeling of drowsiness, uneasiness, taedium vitae, and visual fatigue before and after the maneuver (Table 6).

Table 6

Table 6

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Comparison of scores on the Symptom Checklist before and after the maneuver

Somatization scores on the Symptom Checklist were increased after the maneuver (from 1.47±0.44 to 1.61±0.52, P <0.001), and the scores measuring obsessive-compulsive behavior (from 1.60±0.49 to 1.54±0.52, P <0.05) and psychoticism (from 1.45±0.40 to 1.40±0.46, P <0.05) were decreased. We found no significant difference between the total scores on the self-rated measures or on other subscales (Table 7).

Table 7

Table 7

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DISCUSSION

Military work-related fatigue can severely affect the combat effectiveness of an army. Thus, extensive and in-depth researches1–3 have been conducted in various countries to clarify the pathogenesis of military work-related fatigue. Recent studies in this domain have taken advantage of new scientific and technological achievements to minimize such fatigue in the service of maximizing the effectiveness of the army.

We analyzed the immunological and endocrinological indices of 240 soldiers before and after a large-scale artillery maneuver. The results showed increased heart rates, decreased thyroid functions (T3, FT3, and FT4), and lower levels of testosterone after the maneuver.

The large-scale, intensive artillery maneuver was associated with measurable changes in the neuroendocrinological and immunological functions of the soldiers. Testosterone, a primary anabolic hormone facilitating recovery and protein synthesis after physical activity, is an important androgen in the human body. In controlled conditions, testosterone can strengthen the ability of athletes, and athletic training can also dramatically affect the level of testosterone in the blood.4 The effect of athletic training on the level of testosterone is determined by various factors including the duration and intensity of the exercise and the ability of the body to adapt to the activities. It is widely believed that appropriate athletic training can elevate the level of testosterone in the blood and strengthen the human body, although prolonged and heavy-load training can also lead to overstrain and fatigue in athletes, which tends to cause a decrease in testosterone. Researchers like Tremblay et al5 have found that long and under-load exercise can effectively increase the level of testosterone. Hackney et al6,7 have showed that decreased testosterone in the serum of those who have undergone endurance training played a role in the functional changes of the hypothalamus-pituitary-testicular (HPT) axis. Scholars like Nindl et al8 have reported that decreased testosterone in males who have undergone intensive endurance training is caused by the weakened secretory function of the LH. Animal experiments have confirmed that heavy-load exercises decreased the affinity of LH receptors to rats’ Leydig cells.9 Fellman et al10 have noted that decreased testosterone in the blood of males after long-term exercise might be caused by inhibiting the secretion ability of the testes, and that a compensatory increase in LH was also inhibited at the same time, indicating that long-term and heavy-load exercises can affect the level of the testosterone in serum through regulation of the HPT axis.

Cleare et al11 have compared the changes in the pituitary-adrenal axis of fatigued subjects and healthy volunteers and found that fatigue strengthened the function of the pituitary-adrenal axis in early stage, whereas the main symptom of long-term fatigue was induced by a functional weakening of the adrenal cortex.

When the body is in a state of fatigue, the peripheral circulation levels of TT3 and TT4 are increased to help maintain a higher metabolic rate.12 More T4 is converted to T3, and a state of fatigue leads to an elevated metabolic clearance rate in the thyroid and a decreased level of thyroid-binding globulin. There were no significant differences in the TT4 level in this study. TSH is a major regulator of thyroid function and its level fluctuation was influenced by many factors.13 Our results may be attributable to the influence of feedback from the increased TSH level, an increased conversion of peripheral TSH would ultimately lead to reduced TSH. In the context of normal changes in TT3 and TT4, the change of TSH may not be evident.

The results of the current study were generally consistent with the notion that acute short-term moderate-intensity exercise could activate the immune system and improve immunological function, but long-endurance or long-term intensive training could suppress the function of the immune system. The large-scale and intensive artillery maneuver was associated with a measurable effect on the immune indices of the soldiers. Fatigue led to decreased immunological responses, including decreased humoral immune responses, and might even increase the risk of autoimmune diseases such as Grave’s disease. Additionally, changes in the immune system might ultimately affect the HPT axis through the neuroendocrine-immune system.

Work-related fatigue can affect the function of the immune system of organisms. Indeed, immune system requires the synergistic operation of various immunological cells, including mutual coordination and inhibition among different subsets of T cells and between B and NK cells. The ratio of CD4/CD8 cells is an important indicator of the immunological function of the human body at the cellular level.14–16 It is believed that work-related fatigue is simultaneously transmitted through the HTP axis and the vagal nerve-adrenal medulla axis and is mediated by CD19 receptors on the T lymphocytes of the immune system, but confirmatory evidence has not been found. In the members of lymphocyte subsets, B cells and NK cells play important roles in the humoral immune response.

Early in vitro experiments have reported that NK cells can inhibit the differentiation of B cells. In the present study, the number and activity of NK cells were increased, which would be expected to result in the reduced proliferation, differentiation, and antibody-related responses of B cells.

The levels of catecholamines remain high in human bodies experiencing long-term fatigue. The activities of T and B lymphocytes may be affected by high concentrations of catecholamines, which may reduce the concentration of IL-22 and play a proximal role in the immunodepression of the stress response.17

Furthermore, lasting fatigue can generate enormous physiological and psychological pressure on individuals; some of them may suffer from disorders in psychological activities involving feeling, thinking, and behaving, and then these may lead to symptoms such as depression, fatigue, asthenia, and headaches resulting in lower training proficiency and reduced combat readiness.18,19 This study indicated that a large-scale, intensive artillery maneuver increased unpleasant feelings and somatization scores and decreased scores on psychoticism. Intensive military work can cause the human body to experience fatigue, which may explain the increased somatization scores. Moreover, the soldiers’ concentration on training and the military exercise may explain the decreases in the scores for obsessive-compulsive behavior and psychoticism.

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Keywords:

training fatigue; military operations; endocrine hormones; immune indices; job inventory

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