Per Kristian Opstad

The Effect of Strenuous Exercise, Calorie Deficiency and Sleep Deprivation on White Blood Cells, Plasma Immunoglobulins and Cytokines

Moderate exercise appears to stimulate the immune system, but there is good evidence that intense exercise can cause immune deficiency. In the present study the authors examined the effect of continuous physical exercise (35% of VO2 max), calorie deficiency and sleep deprivation on the immune system of young men participating in a 5–7 days military training course. There was a two–three fold increase of neutrophils from day 1, the values remained high and decreased slightly at the end of the course. Monocyte counts also increased with a pattern similar to that of neutrophils. Eosinophils decreased to 30% of control and lymphocyte numbers decreased by 30–40%. All the major subgroups (CD4 T cells , CD8 T cells, B cells, NK cells) were reduced. Neutrophil function, as tested by measuring chemotaxis, was significantly stimulated during the first days of the course, in particular in the group with the lowest calorie intake. The mitogenic response of lymphocytes to PHA and Con A was variable, ranging from stimulation during one course to no effect in another course. Serum levels of immunoglobulins decreased significantly during the course. IgG was reduced by 6–7%, IgA by 10–20% and IgM by 20–35%. The authors found no changes of interleukin 1, 2 and 4 during the course, but a (12–20%) reduction (P<0.01) of interleukin 6 , and an increase (P<0.01) of granulocyte–macrophage colony stimulating factor. Altogether the results from the ranger course present a mixed‐up picture. The non‐specific phagocyte‐related immunity was enhanced. On the other hand, the data indicate that even a moderate physical activity, around the clock, caused significant suppression of a number of parameters reflecting the status of the specific, lymphocyte‐related immunity. It is noteworthy, however, that there was no significantly increased infection rate during the course or in the first 4–5 weeks thereafter.

Binding of vasoactive intestinal polypeptide (VIP) by human blood monocytes: demonstration of specific binding sites

Vasoactive intestinal polypeptide (VIP) interaction with a 94% pure preparation of monocytes isolated from human peripheral blood was studied by direct binding technique using 3-[125I]tyrosyl-VIP as a tracer ligand. Scatchard analysis of binding data was compatible with two classes of binding sites, one with Kd = 0.25 nM and maximal binding capacity of 16 fmol/10(6) cells, and another one with Kd = 25 nM and maximal binding capacity of 180 fmol/10(6) cells. The binding was time-, temperature-, and pH-dependent and was saturable, reversible, and specific. This study has demonstrated that human monocytes have high affinity/low capacity as well as low affinity/high capacity binding sites for VIP. No specific VIP binding was found in pure preparations of human granulocytes, platelets or erythrocytes.

Elevated VIP and endotoxin plasma levels in human gram-negative septic shock

Vasoactive intestinal polypeptide (VIP) and endotoxin (lipopolysaccharides, LPS) were measured in plasma samples from 11 patients with bacteriologically verified meningococcal disease. Five patients suffered fulminant septicaemia, developed severe septic shock, and 2 died due to circulatory collapse. Initially, all 5 had levels of VIP above 4 pM and plasma endotoxin above 200 ng/liter. Five patients were diagnosed as meningitis and 1 as having meningococcaemia, all with a normal circulatory state. None of these 6 patients had initially levels of VIP above 2.5 pM or endotoxin levels above 25 ng/liter (P less than 0.001). A correlation existed between plasma endotoxin and VIP levels (r = 0.735, P = 0.01). Sequentially collected samples from 3 patients showed rapidly declining VIP levels after initiation of antibiotic and fluid treatment. These results are in agreement with previous animal experiments, suggesting that endotoxin directly or indirectly stimulates the VIP-ergic nervous system in the initial phase of gram-negative septic shock in man.

Altered hormonal response to short-term bicycle exercise in young men after prolonged physical strain, caloric deficit, and sleep deprivation.

SummaryThe hormonal response to a standardized bicycle exercise test was studied in 11 male cadets exposed to a course of 107 h of continuous activity with less than 2 h sleep. The subjects expended about 8,600–11,000 kcal/24 h whereas their daily food intake contained only about 1,500 kcal. The exercise test was performed once 12 days before the course (control experiment) and on day 3 and day 5 during the course, always between 0700–0900 h.A two to six fold increase was seen in the resting levels of noradrenaline, adrenaline, dopamine, and growth hormone during the course whereas a decrease was observed for thyroxine, triiodothyronine, and prolactin. Cortisol increased on day 3 and then decreased to precourse levels on day 5.The response to the exercise test during the course for all catecholamines was a further increase aboye and proportional to the raisted resting levels. Growth hormone increased by about 6–8 Μg/l both before and during the course. During the exercise test, cortisol decreased before the course whereas it increased during the course. All plasma levels of cortisol were higher on day 3 than on day 5 and in the control experiment.The post-exercise insulin increase was reduced during the course corresponding to a reduction in blood glucose levels. Prolactin decreased during and after exercise in the control experiment, whereas on day 5 the opposite response was seen. No changes in the disappearance rate of different hormones were observed during the course.The present investigation has demonstrated that prolonged strain severely affects the resting plasma levels of different hormones as well as the endocrine response to a short-term physical exercise.

The effect of sleep deprivation on the plasma levels of hormones during prolonged physical strain and calorie deficiency

SummaryThe effect of sleep on the serum levels of hormones during prolonged heavy physical strain and calorie deficiency were investigated in 19 young men participating in a 5 day ranger training course with a calorie consumption of 35,000–50,000 kJ·24 h−1, and a calorie intake of about 6,000 kJ·24 h−1. The subjects were divided into two groups: the stress group (8 cadets) were allowed no organized sleep during the course, whereas the sleep group (9 cadets) had 3 h sleep each night.Small but significantly (p<0.01) higher serum levels were found in the sleep group compared to the stress group for cortisol, growth hormone and testosterone. No such differences were found for catecholamines, androstendione, dihydrotestosterone, LH, triiodothyronine and thyroxine.Androstendione and dihydrotestosterone decreased in parallel with testosterone (r=0.5) during the course, changes which directly or indirectly seem to be due to decreased testicular secretion. The changes found during this investigation for the other hormones are similar to changes found during previous courses. LH showed only small variation during the course and cannot explain the decreased secretion from the testis or the difference between the two groups for testosterone. All hormones were normal within 23 days after the end of the course.

The effect of a high calory diet on hormonal changes in young men during prolonged physical strain and sleep deprivation

SummaryMajor changes occur in the serum level of several hormones during 5 days of heavy and continuous physical activities, with less than a total of 2 h of sleep. The present investigation was designed to evaluate the importance of caloric deficiency, energy requirement being about 8,000–10,000 kcal/24 h. A comparison between well fed subjects and those with food deprivation revealed significantly higher levels of (T3) triiodothyronin, insulin and thyroid stimulating hormone (TSH) in the well-fed subjects, who also had lower levels of growth hormone (hGH) and cortisol, whereas no difference was found between the two groups for thyroxin (T4). Increased levels were found for T3 and T4 in both groups during the first day of activity, with a concomitant decrease in TSH and a subsequent decrease of T4 during the next 2 days. T3 decreased only in the low-calory group whereas increased levels were found in the iso-calory group throughout the course. The resting levels of insulin decreased during the course in the low-calory group whereas it increased in the iso-calory group. High levels were maintained throughout the course for hGH. Cortisol showed high levels just before the start of the course and then decreased from day 2 to day 4. No difference was found between the morning and evening levels for cortisol, indicating disappearance of the circadian rhythm. The present investigation has shown that energy deficiency during prolonged physical strain is responsible for the decreased serum levels of T3 and insulin and may contribute to the decrease in TSH and the increase in hGH and cortisol.

Rapid rewarming after mild hypothermia accentuates the inflammatory response after acute volume controlled haemorrhage in spontaneously breathing rats

Accidental hypothermia is a common companion of trauma/haemorrhage, and several clinical studies have identified reduced body temperature as an independent risk predisposing to increased morbidity and mortality. Accordingly, the majority of trauma care guidelines prescribe early and aggressive rewarming of hypothermic patients. Enzyme reactions are generally downregulated at temperatures below 37 degrees C, including most of those responsible for the inflammatory response. The rationale for adhering to these recommendations uncritically may therefore be questioned. In a rat model of mild hypothermia and haemorrhagic shock we wanted to compare the influence of rapid rewarming with persistently reduced temperature on the synthesis of early inflammatory mediators and organ function. Thirty-four male albino Sprague-Dawley rats were studied. Withdrawal of 2.5 ml blood/100 g body weight was performed over 10 min, with simultaneous reduction of body temperature to 32.5-33.5 degrees C. Seventy-five minutes after initiation of bleeding, two-thirds of the shed blood was retransfused. One group (n=17) was rewarmed to normothermia, the other (n=17) was kept hypothermic. The study was terminated after an observation period of 2 h. At the end of the study the rewarmed animals had a significantly lower mean arterial pressure, higher heart rate, higher synthesis of reactive oxygen species from peritoneal phagocytes, increased circulating levels of nitric oxide, and higher values of the organ markers aspartate aminotransferase and urea. The pro-inflammatory cytokines TNF-alpha and IL-6, the anti-inflammatory cytokine IL-10, the organ markers alanine aminotransferase, alpha-glutathione S-transferase and creatinine, as well as organ injury scores were equal in both groups. Three rewarmed rats died prematurely, versus one hypothermic animal. In conclusion, the results suggest that during the early stages after haemorrhagic shock, rapid rewarming from mild hypothermia may have unfavourable effects both on basic haemodynamic variables, and on the internal inflammatory environment of cells and tissues.

Effects of a 3-Month Endurance Event on Physical Performance and Body Composition: The G2 Trans-Greenland Expedition

OBJECTIVE Prolonged physical exertion with inadequate time for recuperation may result in an overtraining phenomenon characterized by reduced physical strength and endurance capacity. We tested the hypothesis that highly motivated men pushed to the limits of their endurance capacity for 3 months would suffer physical breakdown characterized by loss of lean mass and reduced physical performance capacity. METHODS Two well-trained men (VO2max > 60 mL/kg/min), aged 25 years, completed an unsupported, 2928-km, south-to-north ski trek across Greenland in 86 days. The trek involved ski marching, typically for 9 h/d, pulling sleds initially containing 150 kg and a high-fat (60%) energy-dense diet of 25.1 MJ/d. Body composition and physical performance data were collected 14 days before and 4 days after the trek. RESULTS Energy expenditure based on doubly labeled water during three 2-week periods ranged from 28.3 and 34.6 MJ/d in rugged terrain to 14.6 and 16.1 MJ/d during travel on flat terrain for subjects 1 and 2, respectively. Both men lost weight, completing the trek with low-normal fat stores (approximately 13% body fat). The lighter man gained 0.6 kg lean mass, while the heavier man lost 1.4 kg lean mass and a larger amount of fat weight (7.0 kg). Most performance measures showed trivial changes within the errors of measurement and test reproducibility, indicating no loss of endurance capacity, but anaerobic tests (Wingate and vertical jump) were markedly reduced. Markers of metabolic status, including oral glucose tolerance tests, indicated no functional impairments. CONCLUSIONS Although the number of subjects was limited, this observational study demonstrated that well-trained and experienced long-distance ski trekkers who eat an adequate high-calorie diet can perform endurance treks in severe cold, with little or no loss of lean mass and physical capability.

Physical and mental performance of soldiers on high- and low-energy diets during prolonged heavy exercise combined with sleep deprivation

A group of 24 men was studied during a period of heavy, sustained work lasting for 107 hours, during which time they had less than 2 hours sleep. Nine men received a diet providing 33·49 MJ (8000 kcal) and 15 a diet providing 6·30 MJ (1500kcal) per day. The subjects were assessed by objective measurements of simulated military tasks and by subjective assessments using self-rated (Borg perceived exertion and Standford sleepiness scales) and observer-rated scales. Although the high energy group tended to feel slightly more alert there were no differences between the group in the tests of military performance. After 4 days of sustained activity all subjects were judged to be ineffective as soldiers. The high-energy diet was well tolerated. The average loss of body-fat in the high-energy group was 1·3 kg compared with 3·1 kg in the other group, suggesting that even the high-energy group was in energy deficit. These results suggest that the major factor influencing performance in these experiments was sleep de...

Nicotinic acetylcholine receptor activation mediates nicotine‐induced enhancement of experimental periodontitis

BACKGROUND AND OBJECTIVE Smokers have an increased risk of developing periodontitis as well as showing more rapid progression and resistance to treatment of the disease, but the biological mechanisms are poorly understood. Our objective was to investigate putative biological mechanisms by which nicotine may enhance the susceptibility and thus the course of periodontitis in an animal model. MATERIAL AND METHODS Ligature-induced periodontitis was applied in periodontitis-susceptible Fischer 344 rats. The animals were given daily intraperiotonal (i.p.) injections of the nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine (1 mg/kg) 45 min before subcutaneous (s.c.) injections in the neck skin with nicotine (0.8 mg/kg), or treated with the same amount of saline i.p. and nicotine s.c., or with mecamylamine and saline. Control rats received i.p. and s.c. injections of saline only. Periodontal bone loss was assessed when the ligatures had been in place for 3 weeks. Two hours before decapitation, all rats received lipopolysaccharide (LPS; 100 microg/kg, i.p.) to induce a robust immune and stress response. RESULTS Compared with saline/saline-treated control rats, saline/nicotine-treated rats developed significantly more periodontal bone loss, and LPS provoked a significantly smaller increase in circulating levels of the cytokines tumour necrosis factor alpha (TNF-alpha), transforming growth factor 1beta (TGF-1beta) and interleukin-10 (IL-10). Mecamylamine pretreatment of nicotine-treated rats abrogated the increased periodontal bone loss and the LPS-induced TNF-alpha decrease, but had no significant effects on the levels of TGF-1beta and IL-10, or the stress hormone corticosterone. CONCLUSION The results indicate that nicotine enhances susceptibility to periodontitis via nAChRs, which may act via suppressing protective immune responses through the cholinergic anti-inflammatory pathway.