Can they really improve our health? If you are slim, does this mean that your immune system is more resistant to colds and flu infections? Is it safe to play sports during colds? And if all this is true, how many hours a day and what exercises do you need to perform in order to get real benefits from exercise for immunity?
Doctors have made many statements about the positive benefits of exercise for our health, and fitness classes have been approved as an ideal way to achieve these goals. But at the same time, most people blindly follow their set of exercises, not knowing whether their workouts can help improve their health, and not knowing if they are really doing the right thing. According to research, in many cases, too ardent fitness enthusiasts suppression of the immune system due to overly intense training can be diagnosed.
Fitness and immunity
In general, studies of the relationship between health and fitness have shown very positive and promising results. Exercise has some amazing benefits for the body in terms of resistance to infections and certain types of cancer, and perhaps in this way fitness can improve our quality of life. It was found that people who do fitness at an average level of intensity are less likely to have a common cold and other infections of the upper respiratory tract. One study showed that women jogging 35-45 minutes, exactly 5 days a week for 15 weeks less sick with a coldcompared with the control group. 61% of runners also had fewer colds after they started running, and only 4% had a cold.
Another study at the Fred Hutchinson Cancer Center in Seattle showed that moderate physical activity reduces the incidence of colds among overweight people, obesity, a sedentary lifestyle. The training regimen for a group of people consisted of moderate-intensity exercises 5 days a week for 12 months. A recent study from Hong Kong also showed that exercise on low to medium loads leads to lower mortality from complications after the flu. People who practiced at moderate intensities from once a month to three times a week had lower mortality rates. compared to people who have never or rarely practiced exercise.
How does moderate exercise improve our immune system?
Light or moderate exercise fitness boosts our body's natural immune systemProtective cells circulate faster through the body to attack and destroy bacteria, viruses and fungi. Fighters against infection, macrophages, immunoglobulins, white blood cells and other antibodies that are formed in the bone marrow, lungs and spleen, cope with their task faster.
Another theory claims that increasing body temperature during exercise can inhibit the growth of bacteria, reducing their position in the body. Some scientists believe that regular exercise helps not to catch the bacteria and viruses that cause SARS, while other experts believe that physical activity causes the loss of suspected carcinogens through increased sweating.
It is also interesting that active people have lower rates of colon cancer and breast cancer. Researchers believe moderate exercise strengthening the body’s immune system by attacking malignant neoplasms, which are of viral origin. This may also be due to the fact that there is an accelerated passage of food through the intestines.
How many exercises are enough to improve the immune system?
Moderate aerobic activity within 30 minutes almost every day will help to acquire the most positive benefits for the body. Walking fast (about 70% of the maximum heart rate) for 40 minutes a day will strengthen your immunity. Studies have shown that jogging 10 km per week was useful for the immune system of fitness runners, but increasing it to 20 km can, on the contrary, suppress immunity.
Professional athletes are advised to perform one high-intensity training every 2-3 days to ensure their body recovers for 72 hours, when they are more susceptible to infection.
The American College of Sports Medicine talks about its recommended amounts and qualities of exercise for the physical preparation of healthy adults, which meets the requirements for strengthening the immune system. They advise do 3-5 days a week (from 55% -65% of the maximum heart rate) for 20-60 minutes, using any workout that involves large muscle groupssuch as walking, hiking, running, jogging, cycling, dance aerobics, rowing, stairs, swimming, ice skating and other endurance sports.
What can be done to minimize the chances of a cold?
* Carefully monitor your workouts to avoid overtraining and chronic fatigue.
* Not abuse high intensity workouts - such athletes have a higher incidence of SARS.
* Observe well balanced dietto provide the body with vitamins and minerals at an optimal level.
* Use electrolyte drinks before and after endurance exercises or during very hard workouts. The recommended dosage is 30 to 60 grams of carbohydrates during exercise. This reduces the effect of stress hormones on the immune system.
* Get enough sleep. Sleep disturbance may be associated with reduced immunity.
* Minimize stressful situations in life to a minimum.
* Wash your hands with warm water and soap, try not to rub or touch your eyes, nose often, especially during the cold and flu season.
* Do not play sports if you have ARVI to avoid the spread of the virus to other people.
One of the most significant works on the effect of physical stress on immunity (link) was presented in 1994. Based on a number of scientific data, its author Dr. Nyman suggested that the susceptibility of the body to respiratory diseases depends on character workout.
Medium-intensity training gives the body’s immune system more opportunities to resist infections. And if the training is absent or too intense - the risk of getting sick may be higher. Moreover, with a high-intensity training, it can be more than with a complete absence of training.
As a result, Nyman suggested that the ratio of the risks of getting sick and the intensity of training can be represented as J-curve. Since then, this model has often appeared in most of the works on the topic.
Is there any evidence for this hypothesis?
Rather yes than no. And with some amendments. To understand them, let's go further on research and experimentation.
In the first work (link), scientists observed a group of 1,002 people in the autumn-winter period. They found that the duration of the disease and the severity of the symptom correlated with subjects' lifestyles.
For example, those who performed aerobic training 5 times a day generally suffered 43% fewer days than those who did not do it at all.
That is, observation can confirm the left side of the J-curve.
The second work (link), where the authors analyzed the most relevant studies on the topic, indirectly confirmed both parts of the J-curve model. In it, the authors put forward a hypothesis about the mechanism that explains this.
We suggest that regular exercise of moderate intensity can regulate the release of stress hormones to a certain level, which prevents an excessively strong inflammatory response ... and helps activate antiviral immunity.
As for long intensive training, according to the authors, on the contrary, they can give viruses a chance to use the body as a bridgehead for the development of infection and its pathological consequences.
The latest study makes some changes to the J-model, because the adjective is “intensive”, the authors added the characteristic “long-term”. As we will see in many subsequent works, these two characteristics of training will become decisive when it comes to the effect of training on immunity.
1. Do not do 2 days in a row
In a 2016 study (link), a group of subjects performed an intensive crossfit training (strength + gymnastics + cardio) for two consecutive days.
Such a scheme led to decreased immunity, which was expressed in a decrease in anti-inflammatory cytokines in the body of athletes. The authors came to the conclusion that the day after an intensive workout, it is better to set a low-intensity or a day of rest.
4. Exercise regularly
And the most important advice - if you follow the rules above, exercise regularly. In sum, all your workouts give a positive cumulative effect on the immune system, and today it is an undeniable scientific fact. In particular, training increase the immune response viruses, bacteria, and possibly even impede immune aging (link to study).
Moreover, according to recent work, physical activity does not suppress immunity even on a short time horizon after workout.
Note: before the work of 2018, it was believed that physical activity causes a short-term suppression of immunity, and then its functions return to normal. The study questioned this hypothesis, and its authors proposed a series of evidence.
What many studies did not take into account?
There is one simple fact that has not been taken into account in many works: most of the training is carried out in rooms where there are potential carriers of infections and exercise machines that have accumulated a huge number of bacteria. For example, according to a Fitrated study (link) on dumbbells is 362 times more bacteriathan on the toilet lid.
So contrary to the obvious benefits of immunity exercises, going to the gym can be a risk factor. Especially if it is not very clean.
To workout work to strengthen the immune system, exercise regularly, do not put the workout for two days in a row and do not exercise in medium or high intensity for longer than 60-90 minutes per session. And of course, visit the gyms with a small flow of visitors, where they carefully monitor the hygiene and cleanliness of the simulators.
Neuroendocrine modulation of the immune system during exercise and muscle damage
To coordinate the processes of growth and development, the regulation of homeostasis and the body's response to stress, coordinated work of the endocrine and nervous systems is necessary. Science, the subject of which is the study of the relationship between these systems, is called neuroendocrinology. The control of the immune system can be divided into local - carried out using chemical signals generated at the cellular level, and system - through control from the neuroendocrine system. However, there are complex anatomical and physiological interactions between these three systems — the nervous, endocrine, and immune systems (Masek et al., 2003). All three systems are characterized by the presence of receptors for a common set of ligands, including cytokines, peptide hormones, and neurotransmitters (Haddad et al., 2002). Thus, the immune system can affect the neuroendocrine system and vice versa. Exercise is a kind of stress for the body and causes a stereotypical response of the neuroendocrine system to stress, which was first described by Hans Selye as a “general adaptation syndrome” (Selye, (936, p.32). The complexity of the neuroendocrine and immune system is such that it provides variation of the immune response depending on the intensity and duration of exercises, environmental conditions, nutritional characteristics, degree of recovery after previous training and tissue damage (Nicman, 1997, Pedersen, Hoffman-Goetz, 2000).
The purpose of this article is to analyze the response of the neuroendocrine and immune systems to physical activity from various points of view in the context of: a) acute physical activity, b) physical training, c) damage to muscle tissue as a result of regular motor activity. The immune response to acute physical activity is determined by the intensity and duration of the load, the degree of recovery of the body and the presence of nutrients in the body during regular physical activity. In many respects, the response of the body and adaptation in the case of physical training is the cumulative effect of repetitive exercise and resources that are provided to the body for recovery and adaptation. The damage to muscle tissue induced by physical exercise leads to the activation of the immune system at the local and systemic level, and is also a model for studying the inflammatory branch of the functions of the immune system. The neuroendocrine immune response to damage and other stressful effects on the muscles allow us to study the possibilities of the role of this complex system in the induction of adaptations to physical training, in particular in muscle hypertrophy. Understanding the importance of modulation of the immune system due to physical exertion, as well as the possible role of the immune system in the formation of physiological adaptations to physical exercises, is important for the development of training programs for health and sports.
The main components of the immune system (according to Liles, Van Voorhis, 1995, Shepard, 1997, Elenkov et al., 2000, Rivcst, 2001, Suzuki et al., 2002, Steensbcrg et al., 2003)
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They are formed in the bone marrow and circulate in the circulatory system. The bulk binds to endothelial cells of blood vessels, in particular in the lungs
Inflammation and natural immunity against infections. Initiate free radical formation reactions that destroy bacteria and damage neighboring cells. Remove small decay residues in the area of infection or inflammation by phagocytosis
Monocytes are formed in the bone marrow, are found in the blood. Leaving the circulatory system, monocytes differentiate into mature macrophages
Natural immunity against viral infection and tumor cells, phagocytosis of cell decay products, the production of cytokines related to inflammatory processes (TNF-a, IL-ip, IL-6, IL-10, IL-12). After phagocytosis and activation, macrophages are able to present antigens to T-lymphocytes to activate antigen-dependent / acquired immunity
Normal killer cells (NK) (CD3CD16 * CD56 *)
They are formed in the bone marrow, circulate in the blood, bind to vascular endothelial cells in lymphoid tissues
Natural immunity, carried out without recognition of the main histocompatibility complex (MHC), for example, the defeat of cells infected with the virus, and some tumor cells. Essential for protecting against early viruses and certain tumors
Cytotoxic T lymphocytes (CD3 * CD8 *)
They are formed in the bone marrow, mature in the thymus. Mature cells are found in lymphatic tissue, in the spleen and in the blood
Cytotoxicity associated with the recognition of the MHC complex. It is important for the implementation at the cellular level of acquired immunity, which ensures the defeat of infected cells
They are formed in the bone marrow, mature in the thymus. Mature cells are found in lymphatic tissue, in the spleen and in the blood
Coordination of the immune response.Undifferentiated (Th0) CD4 * cells are activated to differentiation by Th1 CD4 * cells, which are responsible for cellular immunity or Th2 CD4 *, which regulate humoral immunity and some inflammation functions. A small number of CD4 * cells producing TGF-P are called Th3 CD4 * cells
They are formed in the bone marrow, after activation by an antigen, they differentiate and turn into plasma cells. Mature B cells are found in many extracellular fluids, including blood and mucous secretions, and accumulate in lymphatic tissues.
Th1 CD4 * T-lymphocyte antigen and cytokine stimulation induces the production of nmunoglobulins (antibodies)
They are produced in plasma cells (B cells activated to produce antigens). Found in blood, saliva, mucous secretions and everywhere in the body
They bind to molecular and cellular antigens a (mi, in particular, bacterial), forming an antibody-antigen complex that induces phagocytosis by neutrophils and macrophages, aimed at eliminating antigen
Th0 and Th1 CD4 * T-lymphocytes, CD8 * T-cells (Tcl subgroup), natural killer cells
It stimulates the activation of macrophages, neutrophils and killer cells, as well as the production of antibodies by B-lymphocytes, and inhibits the production of Th2 cytokine in CD4 T cells
Tumor Necrosis Factor a (TNFa)
It is produced by monocytes, macrophages and killer cells, to a lesser extent neutrophils, T and B lymphocytes and other cells.
Antitumor activity, initiation of the inflammatory process, the involvement of neutrophils and monocytes, as well as the induction of the synthesis of IL-6
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It is produced by monocytes and macrophages.
Induction of cerebral response to inflammation, namely, fever, stimulation of prostaglandin E2 production, stimulation of IL-2 receptor expression, induction of IL-6 synthesis
Th0 and Th1 CD4 + T-lymphocytes, CD8 + T-cells (subgroup Tc1)
Thl cytokine, a potent stimulator of the activity of natural killer cells, stimulation of lymphocyte proliferation and antibody secretion by B cells
Th0 and Th1 CD4 + T-lymphocytes, B-lymphocytes
Stimulation of Th2 cells, stimulation of the production of immunoglobulins and proliferation of B cells, stimulation of the allergic response by production of IgE, inhibition of the production of cytokines YOU CD4 * cells
Th0 and Th1 CD4 + T-lymphocytes, CD8 + T-cells (Tc1 subgroup), monocytes and macrophages, however, almost all cells are capable of producing IL-6, especially muscle cells
Th2 cytokine stimulates the production of immunoglobulins and B-cell proliferation, induction of IL-2 production, stimulation of the acute phase protein synthesis, activation of the hypothalamic-pituitary-adrenal system, suppression of TNF-a and IL-β synthesis, stimulation of IL-10 and IL-lra synthesis
It is produced by monocytes and macrophages, endothelial cells.
Chemokine directs neutrophils to the site of inflammation, stimulates the formation of reactive radicals of the acidic genus and degranulation using neutrophils
It is produced by Th0 and Th1 CD4 * T-lymphocytes, monocytes and B-cells, as well as cells of the hypothalamus and pituitary gland
Th2 cytokine, inhibits the production of cytokines YOU CD4 * T-lymphocytes, monocytes and macrophages, stimulates the proliferation of B-lymphocytes and antibody production
Stimulates the immune pathway Th1, stimulates the activity of CD8 * T-lymphocytes and natural killer cells, inhibits the secretion of IgE by B-lymphocytes
Transforming Growth Factor β (TGF-β)
Th3 CD4 + T cells, macrophages and other cells
Suppression of the activity of killer cells, proliferation of B and T cells, as well as some macrophage function, stimulation of IgA secretion by B lymphocytes
Sympathetic nervous system
The autonomic nervous system includes the parasympathetic nervous system, which controls the functioning of the body at rest, and the sympathetic nervous system, which provides the body with the ability to actively move as in the case of a fast motor reaction to stress (“ftght-and-flight 'response). The response to stress, regardless of its nature, is coordinated by the joint activity of the sympathetic nervous and hypothalamic-pituitary-adrenal systems (Tsigos and Chrousos, 2002). The sympathetic nervous system secretes specific neurotransmitters catecholamines - adrenaline and norepinephrine. Activation of the sympathetic nervous system with the participation of the norepinephrine system (locus ccruleus - blue spot) stimulates the release of adrenaline by the cells of the adrenal medulla and norepinephrine by the ends of the axons of the sympathetic neurons. The concentration of these neurotransmitters in the blood during exercise increases, however, in terms of relative content, norepinephrine exceeds adrenaline by several orders of magnitude (Weicker, Werle, 1991, Kjaer, Dela, 1996). There is a linear dependence of the increase in the concentration of catecholamines on the duration of physical activity (Kjaer, Dela, 1996). At the same time, the dependence of the level of catecholamines on the intensity of exercises is approaching exponential (Kjaer, Dela, 1996).
White blood cell migration
The most significant effect of catecholamines on the immune system is the recruitment of leukocytes from snoring sites. The introduction of adrenaline and norepinephrine in order to increase the body's ability to withstand physical activity or the use of blockade of catecholamine receptors (adrenergic receptors) during exercise clearly indicate that adrenaline (β1- and β2-adrenergic receptor ligand) stimulates the migration of lymphocytes and neutrophils into the circulatory system during exercise (van Titts et al., 1990, Kap-pel et al., 1991, Benschop et al., 1994, Schedlowski et al., 1996). Norepinephrine (a significant hormone for β1- and less significant for β2-adrenergic receptors) has a less noticeable effect on lymphocytes in the circulatory system during regular motor activity compared to adrenaline. Thus, an increase in the intracellular concentration of cyclic adenosine monophosphate (cAMP) due to the binding of adrenaline to β2-adrenergic receptors is the main stimulus directing lymphocytes and neutrophils into the circulatory system (Boxer et al., 1980, Weickr, Werle, 1991, Schedlowski et al. , 1996).
The innervation of tissues in which the formation and accumulation of cells of the immune system occurs, namely: thymus, spleen, lymph nodes, tonsils, bone marrow and lymphoid tissue of the intestine, is carried out by the sympathetic nervous system using noradrenergic and / or neuropeptide Y nerve endings (Elcnkov ct al., 2000). Such direct contact with the nervous system plays an important role in the functional modulation of immune cells, but has a negligible effect on leukocyte migration due to physical activity.
Functional activity of white blood cells
A simplified point of view on catecholamines as substances with a total immunosuppressive effect does not allow us to consider this regulatory system as capable of a more complex set of reactions (Elenkov ct al., 2000). The acute effect of catecholamines on the immune system is more complex and is manifested mainly in the suppression of the Thl system (formation of interleukin-2 - IL-2, interferon-y - IFN-y and regulation of cellular immunity), the absence of a direct effect on the Th2 system (production of interleukins IL-4 , IL-S, IL-6 and IL-10, as well as the regulation of humoral immunity) and the ambiguous effect on the formation of the inflammatory reaction. Part of the inflammatory response to catecholamines is the result of eliminating the inhibition of the synthesis of inflammatory cytokines, which is manifested in the suppression of the synthesis of interleukins IL-2 and IL-12, i.e., stimulation by removing the inhibition. In contrast to acute physical exertion, chronic exposure to catecholamines leads to loss of sensitivity and suppression of the expression of β-adrenergic receptors or other components of cellular signal transmission systems specific for certain cell types (Elenkov et a., 2000). Thus, acute and chronic stress can have various effects on the immune system.
In addition, catecholamines are able to modulate the function of natural killer cells. Both adrenaline and norepinephrine (adrenaline in particular) induce an increase in the number of killer cells in the circulatory system and a decrease in the specific cytotoxic activity of these cells (Schedlowski et al., 1993, Klokker et al., 1997, Kappel ct a., 1998). The decrease in activity is most likely the result of the decrease in the formation of IL-2 and IL-12 cytokines due to the action of catecholamines, which contribute to an increase in the cytotoxicity of natural killer cells.
Since the induction of many cellular reactions is carried out directly by increasing the concentration of the intracellular level of cAMP (Border ct al., 1998), it was suggested that the functional modulation of lymphocytes in response to increased catecholamines is mediated by macrophages and nitric oxide (Rabin ct al., 1996). Evidence for the existence of such a regulatory mechanism was obtained on rodent models (Blank et al., 1997). An example related to the use of acute physical activity in one study (Kappel ct al., 1991) showed that 2 hours after the administration of adrenaline, the specific activity (per cell) of natural killer cells decreases. At the same time, a twofold increase in the number of monocytes was observed and this led to the assumption that prostaglandias produced by monocytes suppress the cytolytic activity of killer cells. In accordance with this assumption, in the case of suppression of the formation of prostaglandins in monocytes by indomethation, there was also no decrease in the specific activity of killer cells. This suggests that the inhibition of killer cell function is not due to direct exposure to adrenaline, but to prostaglandins produced by monocytes. However, there is evidence showing a decrease in killer cell activity even under the conditions of indomethacin use. Ego means that the mechanism considered is far from being realized in all cases.
The hypothalamic-pituitary-adrenal system will transmit signals from the hypothalamus to the adenohypophysis and further to the adrenal cortex (Tsigos, Cltrousos, 2002, Bcishuizcn, Thijs, 2003). In response to various forms of stress, the hypothalamus releases corgi-koliberin (corticotropin-releasing hormone) and vasopressin. Corticoliberin and, to a lesser extent, vasopressen stimulate the production of adrenocorticotropic hormone (ACTH) in the anterior pituitary gland. The main function of vasopressin is to stimulate the absorption of fluid in the kidneys. ACTH as the endocrine hormone through the circulatory system enters the adrenal glands and stimulates the secretion of glucocorticoid hormones in the adrenal cortex, of which cortisol is the most significant. Thus, cortisol is the final product of the hypothalamic-pituitary-adrenal system. Cortisol is an element of the feedback chain and inhibits the secretion of corticoliberin and adrenocorticotropic hormone. As a steroid hormone, cortisol can diffuse across the plasma membrane and bind to intracellular receptors (Rlccardi et al., 2002). The receptor complex cortisol - other glucocorticoids affects the cellular function, mainly stimulating and inhibiting the transcription of various proteins, as well as in a faster way, as in the case of the Ca2 * -dependent mechanism (Buckingham et al., 1996). Cortisol suppresses a significant amount of the immune response and is a key regulatory element that prevents the immune system from excessively intense effects, which can be devastating. For example, if the inflammatory process proceeds uncontrollably, this can lead to extensive destruction of tissues and even to their death (Northoff et al., 1995, Suzuki et al., 2002).
The effect of cortisol on the immune system is manifested in the suppression of immune function, in particular inflammatory functions. For this reason, glucocorticoid analogs are often used to treat inflammation and autoimmune diseases (Ashwell et al., 2000). The binding of cortisol to the intracellular glucocorticoid receptor leads to the activation of the glucocorticoid-dependent element (CRE) and subsequent transformations (Pitzalis ct al., 2002). Of particular interest is the stimulation of annexic I (previously called lipocortin-1) and anti-inflammatory proteins, for example, a 1L-1 receptor antagonist, and the suppression of cell adhesion molecules (CAM) and cytokines involved in the inflammatory reaction (Levine et al., 1996, Pitzalis ct al., 2002).
The activity level of the hypothalamic-pituitary-adrenal system ideally corresponds to the range that, if necessary, provides an effective immune inflammatory response and at the same time does not allow excessive activity of the immune system, which could become destructive for the body. A variety of forms of exercise can cause a chronic increase in cortisol levels and suppression of immune function (Buckingham et al., 1996). For example, immunosuppression associated with depression is associated with increased levels of cortisol (Leonard, Song, 1996). Conversely, with adrenal insufficiency, the production of glucocorticoids occurs in a limited amount, which leads to an increased susceptibility to autoimmune and inflammatory diseases (Buckingham et al., 1996). Pathological disorders that lead to excessive or insufficient production of glucocorticoids are called Cushing's and Addison's diseases, respectively. Within the non-pathological spectrum of activity of the adrenal cortex, individuals with an increased and weakened response to stress (low and high responders) are distinguished based on the value of ACTH secretion in response to stress (Petridcs ct al., 1997, Dcuster et al., 1999), therefore variability in the magnitude of the reaction of the hypothalamic-pituitary-adrenal system to stress and the existence of several factors modulating this variability, which will also be manifested in the variability of the immune response to stress, regardless of the characteristics of the stress effect.
The two-way interaction between the immune and neuroendocrine systems is such that cytokines mediating inflammation, in particular tumor necrosis factor a (TNF-a), interleukins IL-f and IL-6, as well as leukemia-inhibiting factor (LIF), can stimulate hypothalamic pituitary-adrenal system and induce the secretion of cortisol (Mastorakas et al., 1993, Chesnokova, Melmed, 2002, Tsigos, Chrousos, 2002). Leukemia inhibiting factor (LIF) is required for the secretion of ACTH and cortisol in case of inflammation, and may also contribute to the activation of the hypothalamic-pituitary-adrenal system induced by TNF-a and IL-ip (Chesnokova, Melmed, 2000, 2002, Chesnokova et al., 2002). This means that chemical signals that stimulate the inflammatory process also initiate a feedback system that suppresses their own activity. The opposite function of this relationship has also been demonstrated, namely: lymphocytes can secrete most pituitary hormones (Carr, Blalock, 1990), for example, after stimulation with the immunoreactive antigen or IL-12, they produce somatotropic hormone (Malarkey ct al., 2002).
In addition to modulating the functions of the immune system, glucocorticoids play an important role in ensuring the body's ability to respond properly to stress, increasing the likelihood of survival in stressful situations. They inhibit the secretion of sex steroids and growth hormone (Tsigos, Chrousos, 2002), which reduces energy consumption for growth processes that are not essential for survival. Glucocorticoids also inhibit the activity of the hypothalamic-pituitary-adrenal system, resulting in a decrease in the level of metabolism at rest (Tsigos and Chrousos, 2002). To satisfy the energetic needs of tissues exposed to stress, glucocorticoids stimulate gluconeogenesis, glycogenolysis, lipolysis and proteolysis (McMiggau, Hackney, 2000, Steinacker et al., 2004).By stimulating the processes of gluconeogenesis and glycogenolysis in the liver, cortisol helps maintain blood glucose levels and is therefore considered as a hormone that regulates glucose metabolism. In general, all this leads to a halt in growth processes, a decrease in fertility, a decrease in the level of metabolism and energy requirements of the body, as well as an increase in the availability of reserves of energy substrates of the body that were deposited “on a rainy day”.
Glucocorticoids can inhibit the production of many cytokines, including interleukins IL-1, IL-2, IL-3, IL-4, 1L-5, IL-6, 1L-8, IL-10, IL-13, a stimulating factor granulocyte and macrophage colonies (GM-CSF), TNF-a and IFN-a (Ashwell et al., 2000, Riccanli ct al., 2002). At the same time, their effect on the production of cytokines in Thl T helper cells is more pronounced in comparison with Th2 cells: for example, IL-2 synthesis is inhibited much more strongly than IL-10 synthesis (Ashwell et al., 2000). Thus, glucocorticoids are potent inhibitors of cellular immunity and inflammation.
Despite the importance of studying the effects on the immune system of the sympathetic nervous system and hormones of the hypothalamic-pituitary-adrenal system, it should be noted that immunomodulation due to motor activity is the result of the combined effect of many physiological reactions occurring simultaneously or sequentially. Given the complexity of the systems involved, as well as the number of potential factors that can enhance or mitigate the stress effect on the body as a whole, the totality of the possible effects on the immune response seems almost unlimited. Irregular motor activity can cause a temporary redistribution of white blood cells in the bloodstream and body tissues, change the functionality of white blood cells, induce a massive release of molecules that regulate the immune function, cause temporary or prolonged inflammation and, as a result, change the general level of activity of the immune system, which protects the body from infections and cancer cells. The scale of these changes is usually determined by the amount of physical activity, which is usually determined by the intensity and duration of motor activity (McMiggau and Hackney, 2000).
At the same time, the magnitude of the stressful response to which the neuroendocrine immune system has to respond can increase under the influence of additional factors, for example, insufficient recovery from a previous training session (Ronsen ct al., 2002a, 2002b, McFarlin ct al., 2003), lack of carbohydrates ( Nieman ct al., 1998, Green ct al., 2003), hypoxia (Klokker ct al., 1995, Nicss ct al., 2003) and elevated air temperature (Brenner ct al., 1998, Mitchcll ct al., 2002) .
Suppression of various mechanisms of immune defense after intense and prolonged motor activity can increase the susceptibility of the body to various infections. Athletes are most susceptible to infectious diseases, especially diseases of the upper respiratory tract, during periods of intense training and for several weeks after particularly intense competitions, for example after a marathon (Peters, Bateman, 1983, Nieman, 1998). Reports on the incidence of upper respiratory tract diseases in athletes in such conditions vary, however, according to rough estimates, the risk of a disease is approximately doubled. This means that most athletes do not have upper respiratory tract diseases during intense training, but the risk of their occurrence increases significantly (Nieman, 2000). Violation of the training regime or a possible decrease in sports performance during diseases of the upper respiratory tract or other infectious diseases is a significant problem for many professional athletes. Along with this, the data obtained in studies involving athletes may be applicable to other situations associated with the need to overcome significant physical exertion, in professional activities and during rest.
The mechanisms underlying the increase in susceptibility to disease are not yet fully established. At the same time, it can be assumed that some physiological reactions that develop in response to active motor activity may contribute to an increase in the incidence rate. The period of time after intense physical exercise, when there is a decrease in functional activity and the number of lymphocytes, a decrease in phagocytosis with the participation of neutrophils in the nasopharyngeal cavity, as well as a decrease in the level of IgA in saliva and a weakening of antigen-presenting activity, can be considered as an “open window” that allows viruses to overcome the weakened immune defense (Nieman, 2000). The first line of defense against bacterial and viral pathogens, including mucosal immunoglobulins and neutrophil activity of the mucous membrane of the nasopharynx, is weakened after active exercise (Muns, 1993). In addition, after intense physical activity, there is a decrease in the production of immunoglobulin A in the salivary glands (Mackinnon et al., 1989, Mackinnon, Jenkins, 1993, Nieman et al., 2002), which also contributes to the violation of the first line of defense against infections, affecting the upper respiratory tract. A decrease in IgA in saliva is the only indicator of changes in the state of the immune system that correlates with the onset of upper respiratory tract disease (Mackinnon, 2000). The tendency of catecholamines and cortisol to inhibit the type 1 immune response and stimulate the type 2 immune response also increases the likelihood of upper respiratory tract disease. A similar pattern of changes in T-cell activity and cytokine production is unambiguously observed after 2.5 hours of treadmill running (Steensburg et al., 2001). In addition, increased secretion of cortisol stimulates interleukin IL-6, the production of which increases during regular motor activity (Steensburg et al., 2003). Thus, there is a whole range of mechanisms by which, under the influence of intense and prolonged physical activity, the induction of the neuroendocrine and immune systems occurs, providing favorable conditions for the Th2 system and the inflammatory response due to weakening of the YOU system. Such a shift weakens the antiviral defense and can create more favorable conditions for the multiplication of viruses, especially in the upper respiratory tract.
The nature of the relationship between physical training or physical activity and the state of the immune system is determined by the amount of physical activity and, apparently, the possibility for subsequent recovery. There is a consensus that moderate-intensity physical training can stimulate overall immune defense, while intense and intense training can suppress the function of the immune system (Nieman, 1997, Shephard, 1997). Most likely, changes in the function of the immune system caused by physical training are a component of the systemic response to stress, including the response of the neuroendocrine system. Thus, the stress - recovery ratio may turn out to be the main component determining the shift from beneficial to harmful effects in the event of increased stress in physical training.
Cytokine control of muscle response to stress and damage
Muscle cells secrete cytokines under the influence of physical activity, regardless of the presence of muscle damage. According to modern concepts, many cytokines perform regulatory functions and can represent important signals for controlling cellular functions, as well as system signals for the brain, in particular the hypothalamic-pituitary-adrenal system. Thus, the induction of inflammation is only one of the functions in which these molecules participate, in particular IL-6 and LIF, and the production of these molecules in muscle tissue does not depend on the presence of its damage. For example, LIF has a hypertrophic effect on skeletal muscle cells and causes proliferation of myosatellite lithocytes (Spangenburg, Booth, 2002, Grcgorcvic et al., 2002). IL-6 may act as a systemic signal for a decrease in glycogen level in performing muscle cells (McDonald et al., 2003). However, in case of muscle tissue damage, IL-6 and LIF take part in the inflammatory response. As noted above, TNF-a, IL-ip, IL-6, and LIF can stimulate the hypothalamic-pituitary-adrenal system through a negative feedback chain and induce the production of the anti-inflammatory hormone cortisol (Mastorakos et al., 1993, Chesnokova, Mclmcd, 2002, Tsigos, Chrousos, 2002). Unfortunately, the results of studies of changes in the level of LIF under the influence of physical activity are extremely scarce.
The most common type of muscle tissue damage resulting from regular motor activity is characterized by delayed onset muscle soreness, an example of which is muscle pain felt by an individual the day after an unusual activity. Indirect signs of this type of muscle damage are delayed muscle pain, decreased strength, swelling, and increased serum creatine kinase activity (Miles, Clakson, 1994). The inflammatory process induced by physical activity and suggesting the presence of damage to muscle tissue most likely proceeds in the following sequence: a) physical activity or damage to muscle tissue, b) activation of macrophages in damaged tissue, c) isolation of cytokines - mediators of inflammation, d) stimulation of local isolation of chemoattractants, for example, IL-8, e) local production of IL-6, e) stimulation of acute phase proteins by the liver, g) stimulation of the hypothalamic-pituitary-adrenal system, h) leukocytosis and migratory I was leukocytes to the site of tissue injury (Smith L.L., Miles, 2000). Initiate a cascade of inflammatory events of IL-ip and TNF-a, which include the production of IL-6, which in turn stimulates the formation of other cytokines with anti-inflammatory effects and other molecules, including IL-10 and IL-1ra (Turnbull ct al., 1994, Smith LL, Miles, 2000). Local IL-ip production has been demonstrated in muscle biopsy specimens after performing eccentric physical exercises that led to tissue damage (Malm et al., 2000). However, in the blood, the level of short-lived and relatively small compared with other cytokines increases, in particular, IL-6 and IL-10 (Shepard, 1997, Suzuki et al., 2002), IL-ip and IL-6 can act in the role of growth factors, stimulating regeneration processes at the site of muscle tissue damage (Northoff et al., 1995).
In the inflammatory process, one of the factors determining the possibility of regeneration is the removal of damaged cell debris by phagocytes. The cellular response to exercise-induced muscle damage includes macrophage infiltration into tissue, as well as activation of locally located macrophages (Stupka et al., 2001, LaPointc ct al., 2002). Infiltration of damaged neutrophil tissue was found in some (Brickson et al., 2001, MacIntyre ct al., 2001), but not in all studies (LaPointc ct al., 2002). Muscle biopsy results suggest that this process takes several weeks (Lieber, 1992). This period, undoubtedly, exceeds the time of existence of any detectable markers of inflammation in the circulatory system. Thus, many changes in response to physical activity-induced muscle damage occur more likely at the level of local tissues, rather than the entire body.
If physical exercises have a longer duration and load intensity or are associated with significant mechanical stress for the muscles, for example, in the case of exercises containing eccentric components that require considerable effort, it can be assumed that tissue damage will occur and components of the response described above can be recorded. Marathons and similar loads are accompanied by skeletal muscle damage, which manifests itself in a violation of the structural organization of myofibrils and the release of intracellular creatine kinase from the muscles into the blood (Rogers et al., 1985, Warhol ct al., 1985). After races comparable in scale to a marathon, there is an increase in serum or plasma levels of TNF-a, IL-ip, IL-6, IL-10 and IL-1ra (Northoff et al., 1994, Drenth et al., 1995 , Nehlsen-Cannarella ct al., 1997, Ostrowski ct al., 1998a, 1998b, Henson et al., 2000, Nieman ct al., 2001). Exercises involving more forceful eccentric movements also lead to muscle damage (Fridcn, Lieber, 2001) and a less significant increase in the concentration of IL-ip, IL-6, IL-tra (Bruunsgaard et al., 1997a, Smith LL et 1., 2000, Chen, Hsieh, 2001, Toft ct al., 2002). However, an increase in the level of TNF-a, as a rule, is not observed (Bruunsgaard et al., 1997a, Toft et al., 2002), however, this may reflect the difficulty in assessing the systemic response to a local inflammatory process, which is usually small. A prolonged inflammatory process in the muscles is not accompanied by an increase in cortisol levels (Pizza et al., 1995, Lcnn et al., 2002). Thus, under suitable conditions, the inflammatory response to muscle tissue damage is not strong enough to stimulate the hypothalamic-pituitary-adrenal system for a long time. At the same time, there are neuroendocrine and immune mechanisms of activation of cytokine otpet to damage to muscle tissue, which allows stimulating the hypothalamic-pituitary-adrenal system in case of sufficient production of IL-6 and, possibly, TNF-a, IL-ip and LIF.
The hypothalamus uses the neuroendocrine-immune system to integrate stress signals caused by exercise and central nervous system signals to induce an appropriate response to this stress (Steinackcr et al., 2004). Recent muscle biopsy data suggest that there is a correlation between increased levels of cortisol in the blood and activation of proteolysis in damaged muscle (Willoughby et al., 2003). The response to physical activity is mediated by the ubiquitin-proteolytic pathway, and cortisol enhances the expression of a number of components of this signaling pathway, for example, ubiquitin-a, ubiquitin-ligase and glucocorticoid receptors. If, after one exercise, a defensive reaction is observed, then after the second exercise with the implementation of similar traumatic muscle tissue exercises, the function of the defense mechanisms is suppressed. Thus, the bilateral information exchange system includes cytokine signals generated locally and entering the hypothalamic-pituitary-adrenal system, and signals from the hypothalamic-pituitary-adrenal system, generated in the central nervous system and transmitted to the muscles to trigger repair and regeneration processes in response to tissue damage.
The role of mediators of the inflammatory response in response to exercise-induced damage to muscle tissue was questioned by the results of studies in which, when using anti-inflammatory drugs, it was not possible to detect a noticeable effect on delayed muscle pain or restoration of muscle function (Cheung et al., 2003). At the same time, the work mentioned above is only a small fragment of the results of the study of the role of various components of the inflammatory response in response to physical activity, so it is prudent to simply assume that prostaglandin 11, which is the main target of anti-inflammatory drugs, does not play a significant role in the inflammatory response (Semark et al ., 1999).As a result, anti-inflammatory therapy does not affect the healing process of injuries and only has a weak effect on muscle pain (Cheung et al., 2003).
The immune and neuroendocrine reactions to stress caused by motor activity are undoubtedly interrelated. However, the modulation of the immune response to physical activity is influenced by the inflammatory response to tissue damage. Cytokines, which mediate a local and systemic response to physical activity, often perform several functions in the body; interleukin IL-6 can be cited as one such example. Many functions of these cytokines are not related to the inflammatory response or modulation of the immune response as such, for example, LIF can act as a growth factor without any connection with damage to muscle tissue. The system of bilateral information exchange between the neuroendocrine and immune systems is such that cytokines produced by the muscles can activate the hypothalamic-pituitary-adrenal system. The mutual regulation of the neuroendocrine and immune systems is extremely complex. Nevertheless, experimental data clearly indicate an increase in immune function under the influence of short- or long-term exposure to moderate-intensity physical exercises. The amount of physical activity that the body can withstand without suppressing the immune system and increasing susceptibility to diseases most likely varies depending on the degree to which it is exposed to other stress factors. The data from a number of studies demonstrate the suppression of the function of individual components of the immune system and an increase in the frequency of diseases of the upper respiratory tract in athletes under extreme physical stress during training and competition. Given the peculiarities of the interaction of the neuroendocrine and immune systems, those who wish to maximize the volume and intensity of the training load, we can recommend weakening the response to stress by ensuring adequate recovery of the body and the use of various diets, as well as reducing other forms of stress on the body.
Activity, blood circulation and immunity
Among other things, the lack of physical activity directly affects blood circulation throughout the body. It affects not in the best way: when the muscles do not work, the “active breathing” does not work either - we stop breathing, as they say, “full breasts”.
Why is it important? The fact is that in the absence of "active breathing" the cilia on the epithelium of the mucous membrane of the respiratory tract cease to fulfill one of their important functions - to prevent the penetration of small foreign bodies (whether it be bacteria or just dust particles). As a result, any microorganisms that enter the bronchi and lungs with respiration can easily settle on the mucosa. Because of this, the resistance to infections is sharply reduced, and we become defenseless against diseases.
But it's not only that. It has long been proven that even moderate physical activity (not only training in the gym, but also walking and just everyday movement in a sufficient amount of about 15,000 steps per day) activates the production of T-helpers: lymphocytes, the main function of which is to strengthen the immune response. It is the T-helpers that provide us with primary protection against any viral infections.
In addition, when the muscles are actively working, blood circulation improves, which means faster and more efficient delivery of oxygen and nutrients to all cells of our body. Finally, physical activity helps to balance the functioning of the various components of the immune system - which allows you to more effectively deal with inflammation, diseases and even allergic reactions.
True, in order to achieve such a result, you need to engage regularly. The exception is if you still get sick: in this case, you need to postpone your workouts until they recover completely (and not weigh yourself so as not to get upset where you don’t need to), and you should resume them gradually.