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|Year : 2009 | Volume
| Issue : 44 | Page : 151--155
Is there evidence that environmental noise is immunotoxic?
Audiology Department, Royal Surrey County Hospital, Guildford, Surrey, United Kingdom
Audiology Department, Royal Surrey County Hospital, Guildford, Surrey
Noise is a stressor. Noise-induced stress can lead to release of stress hormones. Acute stress whether physical or psychological is necessary for adaptation to change. However, chronic stress can lead to the persistent elevation of hypothalamic-pituitary-adrenocortical hormones, which are detrimental to health and can lead to disease states. It has also been suggested that there may be multiple interactions between the sympathetic and the complex feedback neuroendocrine systems, which interact with the immune system, in the genesis of the observed effects. Thus noise stress may be a factor contributing to the mechanisms of noise-induced hearing loss through alterations in the cell-mediated immune response. Other than the noise stress acting directly, it may also have an impact on the immune function via noise-induced sleep deprivation. Furthermore, recent evidence indicates that the immune function may be modified by conditioning techniques, perceived control, or the individual's ability to cope with stress-inducing factors. This suggests a possible means of alleviating the stress-induced effects. This review will examine the current available data on the effects of chronic environmental noise exposure on immune function.
|How to cite this article:|
Prasher D. Is there evidence that environmental noise is immunotoxic?.Noise Health 2009;11:151-155
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Prasher D. Is there evidence that environmental noise is immunotoxic?. Noise Health [serial online] 2009 [cited 2022 Sep 30 ];11:151-155
Available from: https://www.noiseandhealth.org/text.asp?2009/11/44/151/53361
What is stress? Stress has its origins in "distress" and is considered to be a short form for it. Distress is defined by the Oxford English dictionary as a state of extreme anxiety or suffering and stress as a state of mental, emotional, or other strain.
In physics, stress is defined as the internal distribution of forces within a body that balance and react to the loads applied to it. Stress as a medical term was first described in 1936 by Hans Selye  in the journal 'Nature', in terms of a wide range of strong external stimuli, both physiological and psychological, which can cause a physiological response, which he termed "the general adaptation syndrome." As the term had been quite loosely defined, Chrousos  defined stress as "an animal's state of threatened homeostasis" (an organism's ability to maintain a steady internal state).The disturbing forces or threats to homeostasis are called stressors and the counter-balancing or re-establishing forces are called adaptive responses. The body responds to the external and internal environment by producing hormonal and neurotransmitter mediators that provide coordinated physiological responses to the prevailing circumstances. The measurement of the physiological responses of the body to environmental challenges constitutes the primary means of relating the environmental impact on health. As the subjective experiences of stress do not always correlate with the output of the physiological mediators of stress,  measurement of the physiological responses of the body to the environmental challenges provides a means of relating the effect of environment to the risk for disease. Secretion levels of the hormones such as cortisol and catecholamines, not only vary due to stress factors, but they also show a variation according to a diurnal rhythm that is coordinated by the light-dark cycle and sleep-waking patterns.
A concept of allostasis, literally meaning "maintaining stability (or homeostasis) through change," was initially introduced by Sterling and Eyer in 1988,  to describe how the cardiovascular system adjusts to the resting and active states of the body. This notion has been applied to other physiological mediators, such as the secretion of cortisol as well as catecholamines, and the concept of "allostatic load" was proposed to refer to the wear and tear that the body experiences due to repeated cycles of allostasis as well as the inefficient turning-on or shutting-off of these responses. , The concept of allostasis and allostatic load is based on a cascade of cause and effect that begins with primary stress mediators, such as, catecholamines and cortisol. Allostasis has evolved as a response for the flight-fight-freeze defense cascade. These responses, according to phylogenetic origins, are designed to run away from a predator or fight a threat. The brain provides redistribution of energy to parts of the body that need it most to meet the demands of the situation. This system also provides higher levels of stress hormones in the morning to deal with the challenges of the day and is low at night. However, this archaic system of defense persists in this modern world with new demands, which may not require the repeated activation of stress mechanisms. Thus if the allostatic load becomes too high, a state defined as the permanent initiation of the warding-off of stress may result in disorder prevailing in terms of excess eating or loss of appetite, aches and pains, sleep disturbance, memory disturbance, and so on. A long-term high allostatic load may lead to damage of the organs including the brain. Allostasis starts with the signal from the hypothalamus deep in the brain to the adrenal glands above the kidneys, which then release major stress hormones. The hypothalamic-pituitary-adrenal (HPA) axis is the major route forming the cascade, which deals with the stressor from external or internal sources. If the stress is unremitting the balance in energy provided by the HPA is disturbed thereby tilting the axis toward over- or underactivation, either of which may initiate conditions favoring disorder. The primary targets for stress hormones in the brain are hippocampus and the amygdala where neuronal alterations can lead to problems of memory, learning, and emotions. Thus stressful events and experiences can activate a variety of responses designed by evolution to avoid danger, but chronic exposure to stressful events may lead to dysregulation of HPA defense mechanisms, resulting in stress-induced disorders.
Noise is a common physical nonspecific stressor. Similar to other stressors, it disturbs the homeostasis of the cardiovascular, endocrine, and immune systems in the body to cope with the environmental or perceived demands of the individual. The imbalance between the demand and the individual's resources to cope determine the individual's ability to deal with noise-induced stress. The body's inability to deal with overstimulation can lead to adverse stress reactions. A recent study  points to the fact that the neuroendocrine response of subjects exposed to low-frequency ventilation noise are similar to other stressors.
Acute stress requires a rapid response from the body in terms of a fight or flight response, to deal with the real or perceived threat in the immediate environment. In the case of noise, an unexpected loud noise or an unusual nature of noise may trigger a fight/flight reaction via the hypothalamus, with increasing levels of adrenalin and oxygen uptake to the brain and reduced activation in other areas. The adrenal medullary system is activated by the sympathetic nervous system to secrete adrenalin and noradrenalin. Elevated adrenalin levels increase heart rate, cause vasodilation of the arteries in the muscles and the brain, and cause an increase in the release of glycose and lipids in the blood. Noradrenalin controls blood pressure with redistribution of blood from the skin and the gastrointestinal system to the muscles, heart, and brain. These responses are fast and are designed to relieve the threat rapidly and effectively. The HPA axis is activated by hormonal signals from the brain. The pituitary responds with the adrencorticotrophin hormone (ACTH), which in turn activates the adrenal cortex to secrete cortisol. Cortisol affects the metabolism in the cells and plays an important part in the regulation of the immune system responsible for anti-inflammatory effects. In the acute stress reaction to an immediate threat, the secretion of stress hormones results in increased heart rate and blood pressure, a rapid release of energy in the blood stream, reduced metabolism with a decrease in salivary and gastro-intestinal activity, reduction in sex hormones, and activation of some immune functions. There will also be a reduction in pain sensitivity, focusing of mental activity and memory functions, and improved vision, to deal with the threat. The increased energy to the brain, heart, and muscles will also allow the individual to better deal with the threat. Thus significant changes occur in body functions to allow the individual to both physically and mentally deal with the current threat and consolidate for similar threats in the future with enhanced memory functions. Acute stress reaction is necessary for survival, but if such stress-mediated reactions occur repeatedly or with chronic presence of stress reactions, there may be adverse effects on the individual from the imbalance in the response of the body systems. During short-term stress there is enhanced immune activity, whereas, during long-term stress there may be impairment of immune activity. Cessation of the acute stress reaction from the perceived or real threat is necessary for recovery and rest, but if overstimulation due to chronic stress reaction continues, it may be damaging to the health of the individual. The activation of certain body systems to a more heightened level and the diminution of activity in others, mean that if stress reactions are chronic, areas of reduced activity, such as, the gastrointestinal system, skin, sex, sleep, and response to infections may be adversely affected.
Chronic noise exposure leading to hormonal changes may be particularly important in adverse reactions and development of disease states. This model of reactivity in terms of noise-induced stress has been implicated in the development of disorders of the cardiovascular system, sleep, learning, memory, motivation, problem-solving, aggression, and annoyance.
Noise Stress and Cortisol
According to the psychophysiological stress model of Henry and Stephens  the perceived stimulus, depending on the individual's coping resources and early experience and genetic background will determine whether there is a perceived threat to control or loss of control. This will determine which path is taken, a) flight/fight path, which will result in an increase of adrenalin and noradrenalin via the adrenal medullary and sympathetic pathways or b) the defeat path, which would increase ACTH and cortisol via the hypophysis and adrenal-cortex route. A number of studies have shown a relationship between noise-induced stress and the level of glucocorticoid hormone cortisol secretion during and after noise exposure. Cortisol levels can be measured not only in urine and serum, but also in saliva. The concentration of cortisol in saliva has been shown  to reflect the concentration of free physiologically active cortisol in serum. Salivary cortisol is an inexpensive and reliable measure of bioactive cortisol in the body. Cortisol is a stable molecule in saliva and can be stored for at least four weeks without degradation in level.  Cortisol levels have been interpreted as the allostatic load  or homeostatic response of the body,  but due to the large inter-individual and intra-individual diurnal variation, it has been difficult to use cortisol measurements in large-scale studies as a number of measurements per day per individual were deemed necessary. However recent work  has shown that repeated assessment of the awakening cortisol response can serve as a more useful index of adrenocortical activity. Waking up in the morning is a potent stimulus for the HPA axis,  as within the first 30 minutes of awakening the cortisol levels rise by 50-60% in about 80% of the people and remain elevated for 60 minutes. , The basal level at this time of the morning shows considerable intraindividual stability over days. This response has been found to be unaffected by the time of awakening, total time slept, physical activity, or morning routine. Furthermore, the free cortisol response at awakening appears to uncover subtle changes in HPA activity, as the magnitude and time course have been shown to be influenced by gender, persisting pain, burnout, and chronic stress. ,
Both acute and chronic exposure to noise can affect cortisol levels. ,, Traffic noise can cause stress reactions with increased concentrations of stress hormones in the blood  and noise-induced stress effects on cortisol can occur during sleep, which can develop into a chronic increase if noise exposure is repeated. , A review of studies since 1987 has been presented by Ising and Braun.  Noise-induced stress causing a change in cortisol has been observed in rats, fish, pigs, and humans. Workers exposed to occupational noise  show higher cortisol after a day's work than the control group, but no relationship between level of noise and serum cortisol level has been observed. The relationship between the noise exposure level and cortisol level is not clear, as a high noise level may act directly as a stressor, but low levels may also affect cortisol secretion depending on the meaning and disturbing nature of the stimulus rather than its level. Sapolsky  has discussed the possibility of high cortisol concentrations causing partial destruction of cortisol receptors in the brain, which in turn may be responsible for the chronic elevation of cortisol with long-term side effects of arteriosclerosis and immunosuppression. The cortisol levels usually show a diurnal variation with high levels in the morning and low at night. This cyclic variation can also be disturbed by chronic exposure to stress-inducing stimuli, including noise. Thus, the regulatory mechanism of cortisol can lead to enhancement of cortisol levels with chronic exposure, with no downregulation at night. It has been suggested that prolonged stress due to chronic noise may lead to an inefficient regulation of cortisol levels. Thus it appears that high or low levels of cortisol without significant diurnal variation may be a risk factor in inducing stress-related disease states. The rhythmic regulation of cortisol is an important factor in dealing effectively with physical or psychological stress. Mental work under noisy conditions can enhance cortisol levels  and industrial workers who are exposed to high noise levels fail to show circadian decline in cortisol, but after wearing ear protection, their afternoon cortisol levels decline. 
There is growing evidence that noise can affect the HPA function, and therefore cortisol levels, acutely as well as chronically. It may be valuable to include the salivary cortisol measure in noise research to examine noise-induced stress or allostatic load and perhaps susceptibility to disorders.
Noise Stress and Sleep Disturbance
Exposure to noise, particularly when it is unpredictable and intermittent can lead to noise-induced sleep disturbance. The pathway of noise-mediated sleep disturbance is not clear, particularly if noise exposure occurs during daytime and the nocturnal sleep architecture is disturbed. It may be postulated that noise exposure activates a stress response that affects the sleep in these individuals. Ising and Braun  have shown that lower levels of noise exposure can trigger stress effects during sleep, compared to active conditions. They postulated that during sleep there is no active reasoned interpretation of the noise but a primordial response to an impending danger signal. The implication of this is that the level of noise cannot be a predictor of a stress reaction but the associated meaning of the noise for the individual.
The diurnal variation in cortisol with a minimum during early sleep with predominance of slow wave sleep (SWS), with maximum levels during late sleep, during rapid eye movement (REM) sleep. It appears that there is an active inhibition of the stress system during early sleep according to Born and Fehn (2000),  to allow formation of memories in sleep. Furthermore, they suggest that the suppression of pituitary-adrenal secretary activity during early sleep can be significantly weakened after profound acute stress, as also in a state of chronic stress (including normal aging), which thereby disturbs the regular memory formation in sleep.
A recent study  examined the effect of acute exposure to loud occupational noise during daytime on the nocturnal sleep architecture, heart rate during sleep, and serum cortisol levels in healthy volunteers. They showed that sleep efficiency was 80% and the total time spent in REM sleep, SWS, and the REM onset latency was significantly decreased on the night after exposure to noise. There was an increase in stage shifts. The percentage fall in heart rate during sleep was decreased compared to baseline values. The serum cortisol levels in the morning, after exposure to noise, were significantly increased. Other studies , have shown that prolonged exposure to loud noise causes an increased stimulation of the symapthoadrenal system. As many discrepancies exist in the literature pertaining to noise-induced sleep disturbance, Rabat et al .  have shown in a validated animal model that chronic exposure to environmental noise restricts the amount of slow wave sleep and paradoxical sleep, and fragments these two stages, with no habituation. There is a variation in rats in terms of the deleterious effects on slow wave sleep, which is related to their locomotor reactivity to novelty, and is a behavioral measure of reactivity to stress. This implies that the psychobiological trait (or stress factor) of an individual may determine the vulnerability of individuals to environmental noise effects, particularly on sleep restriction, and its consequence in terms of inducing memory deficits.
It is clear that glucocorticoids such as corticosterone and cortisol inhibit slow wave sleep, although large individual differences of the HPA axis in response to stress exist. Noise activates the HPA axis, which in turn may have an effect on sleep disturbances and long-term memory deficits, and adaptive responses to stress may be inefficient for some individuals and therefore facilitate the vulnerability to noise effects. The implication is that high reactive rats may develop noise-induced stress effects.
Noise Stress and Immune Function
The immune system protects the body from disease organisms and other foreign bodies, known as antigens. The skin, peritoneum, and so on, form the first line of defense as local barriers and immunoglobulins, or antibodies act against inflammation. If these fail to block or destroy the antigens, the cell-mediated immune response and the humoral immune response (HIR) is initiated. The cell-mediated response uses sensitized T cells (white blood cells derived in the thymus) to recognize, attach to, and render antigens inactive. Other types of T cells, helper T cells, which aid in the production of antibodies by B (bone marrow) cells, and suppressor/cytotoxic T cells, which inhibit that production, are also essential for proper immune system function. Helper T cells are also known as CD4 cells, and suppressor T cells are known as CD8 cells. Studies by Manuck et al .  showed that psychological stressors induced cell division among CD8 cells, thereby increasing the number of CD8 cells and suppressing the immune function. However, this response was only seen in those subjects who also showed high heart rate change and catecholamine change during the stress.
This indicates that there are two groups of people, those who are "high reactors", and those who are "low reactors". High reactors are significantly affected by stress, as shown by a significant increase in heart rate, blood pressure, catecholamines, and CD8 cells. Low reactors show little or no change in those areas. Furthermore, in a stress-mediated alteration in HPA axis activation, with increased catecholamines, there is evidence that these actions suppress aspects of immune function, including natural killer cell (cells that attack antigens without having recognized them first) activity. An increase in catacholemines may also rapidly alter cell numbers via redistribution. In fact, changes in adrenaline levels are thought to reflect lymphocyte migration from the bone marrow, the extremities, and the thymus  to other areas of the body.
Stress has also been shown to increase susceptibility to viral infection. Subjects exposed to stress showed an increase in infection rates from 74 to 90%, and clinical colds rose from 27 to 47%. Earlier studies have shown that medical students have an increased risk of mononucleosis during examination periods.  This is not surprising, as stress does suppress the immune system; latent viruses then have an easier time resurging, since the body cannot defend itself as well.  Additionally, studies on monkeys have shown that ulceration showed up most severely during the rest and recovery periods, rather than during the stress period itself. 
Thus it appears that chronic stress with a continuous release of stress hormones leads to a raised threshold at which immune function is activated, thereby allowing reduced immunity from infections.
Stress and Disease
Chronic stress seems to impair the immune system's capacity to respond to glucocorticoid hormones that are normally responsible for terminating an inflammatory response. It raises catecholamine and CD8 levels, which suppress the immune system, and raise the risk of viral infection. Stress also leads to the release of histamines, which can trigger severe broncoconstriction in asthmatics. Stress increases the risk of diabetes mellitus, especially in overweight individuals, since stress alters insulin needs. Stress also alters the acid concentration in the stomach, which can lead to peptic ulcers, stress ulcers, or ulcerative colitis. Chronic stress can also lead to plaque buildup in the arteries, especially if combined with a high-fat diet. This buildup is called atherosclerosis, and is often responsible for angina or heart attacks, which are usually brought on by acute stress. These diseases are by no means the only ones connected with stress, although they are the most common. Further research is needed to clarify exactly how stressors contribute to each of these problems, so that treatment can be given to protect the body from these diseases.
It is clear that noise is a stressor. The physiological response to noise as a stressor is no different from any other nonspecific physical stressor. The acute and chronic responses of the HPA system are variable across individuals to noise as well as other stressors, but it is clear that a sustained activation of the HPA system causes imbalance of the hormonal system and promotes disorders of many organs including the brain. Saliva cortisol as a measure of the stress-activated HPA function provides a simple and effective means of determining the reactivity of HPA, and as a result, an individual's vulnerability to disease. The stress-mediated suppression of the immune system may also increase the individual's risk for acquisition of disease. Thus noise as a stressor may be a contributory factor in an individual's allostatic load, affecting their health.
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