Regular exercise reduces the risk and increases the chances of a favourable outcome in a number of chronic conditions such as cardiovascular, cardiovascular diseases and diabetes mellitus. However, it has also been shown that intense exercise can be detrimental in that it can cause acute myocardial infarction, pre-mature ventricular depolarisation and a general increase in the risk of cardiovascular death. There is, therefore, a need to define the amount of exercise that can be beneficial without causing any undue disadvantage.
In the recent years, curiosity regarding the mechanisms of inflammatory processes has been on the rise due to ever increasing cases of immune suppressed individuals (e.g. elderly, HIV, other immunocompromised diseases, induced suppression of immunity for organ transplantation, development of antibiotic resistance, sepsis due to surgery or trauma and cancer therapy). Also, it is a major cause of morbidity and mortality in post surgical, trauma, burns or blood loss patients. Furthermore, uncontrolled sepsis forms the basis of multiple organ failure. One of the difficulties has been the prevention and reversal of a systemic inflammatory response.
Although there have been dramatic advances in critical and surgical care, sepsis still poses a major concern in the management of these patients. This is so mainly due to the little progress made regarding the understanding of the underlying immune mechanisms. And part of the reason is that there has been a lack of appropriate human experimental tools. Animal model have not been helpful because of interspecies differences and gross differences in the cellular physiology of the immune system. A study conducted in 1994 has noted that there is a marked similarity between the immune responses to surgery or trauma and those occurring in reaction to a single stress of exhaustive exercise or prolonged heavy training. Exercise induced immune response has therefore been suggested as a model for further research into immune mechanisms.
Overtraining is a subjective term. It means underperformance in an athlete accompanied by a general feeling of fatigue. This is caused mainly by the stress of training, be it physical or psychological. There is an alleged increase in the susceptibility to infections which is indeed reflected by short term elevation of the so called markers of exercise.
Overtraining, contrary to popular belief, is quite common. It occurs in 10-20% of elite endurance athletes. It has been referred to by various terms by different researchers: burnout or staleness, sports fatigue syndrome, chronic fatigue syndrome or simply, unexplained underperformance syndrome.
However, there is no consensus as to the definition and the diagnosis of the condition. The round table meeting held on 19 April 1999 at St. Catherine’s College, Oxford came up with the definition and basis for diagnosis of chronic fatigue syndrome. Over training was defined as persistent unexplained underperformance by an athlete which is recognised and agreed to by both the athlete and the coach and does not resolve in spite of two weeks of relative rest. It is characterised by undue and uncharacteristic fatigue and sweating during training. There is a positive history of recent heavy training or participation in an important event, frequent minor infections, unusually stiff or sore muscles, loss of appetite, energy, drive, competitive edge, and mood and sleep disturbances.
Overview of the human immune system
The human immune system is divided into the innate or the inborn immunity which is present since birth and the acquired immunity which develops subsequently as the exposure to various antigens takes place during the lifetime of the individual.
Evaluation of the response to exercise
Traditionally, various studies have tried to suggest the direct relation of various parameters to overtraining viz. low Hb and ferritin concentrations, elevated uric acid, creatine phoshokinase and cortisol levels. Likewise, the increase of immune response in the form of increase in immune cell counts and elaboration of chemical mediators of inflammation has also been associated with exercise. But, concrete proof regarding definite association and mechanism of overtraining has been lacking. Treatment is in the form of relative rest and stress management.
Differential WBC count
This is a measure of the status of the immune system. The leucocytes consist of the polymorphs, and the mononuclear cells. These can be measured with the use of monoclonal antibodies. The peripheral leucocyte count during exercise can be influenced by other factors like increase in cardiac output, decreased plasma volume, stimulation of the autonomic nervous system and secretion of cortisol.
The exercise related increase in leucocyte and lymphocyte levels in the peripheral venous blood is directly proportional to the intensity and the duration of exercise undertaken. However, prolongation of the exercise leads to the migration of the monocytes and NK cells into the injured muscles and therefore a decrease in the total leucocyte count. Subsequently, there is delayed leucocytosis after about 30 min. to 3 hour following strenuous exercise. This is due to the release of cortisol and the cortisol induced secretion of white blood cells from the bone marrow. This involves granulocytes, esp. neutrophils. There is little change in the basophils while the eosinophils decrease in number. This response of the WBCs is rather vague but there seems to be an enhancement of the nonspecific immunity.
Lymphocytes are divided into two distinct types, the T cells and the B cells. These cells are responsible for cell-mediated immunity. The T cells are further sub typed according to the surface antigens present on them. The ratio of helper to suppressor T cells (CD4:CD8 ratio) is important, in the sense, that if the ratio falls below 1.5, it represents an immunodeficient state of the individual and resultant increased susceptibility to infection. Using modern monoclonal antibody techniques, it has been shown that there is an increase in the absolute number of both T and B lymphocyte following submaximal exercise.
There is a drop in the helper: suppressor cell ratio in the early stages. This is mainly due to the increased up regulation of the adrenoreceptors on the T cells than on the B cells. In the latter part of the recovery, occurring over 24 hours, elevation of the ratio occurs due probably to the cortisol induced reduction in the number of suppressor cells. Furthermore, this also suppresses the level of natural killer cells.
Natural killer cells, also called the NK cells, do not require prior sensitization to destroy tumor and virus cells. They form a part of the first defence mechanism of the immune system. These are identified using antibodies to CD16 and CD56 surface markers. The lytic activity is assessed using radioactive chromium-release assay. Increased lytic activity is a measure of either increase in the number of NK cells or increased activity of the individual NK cells.
In the early stage of moderate exercise, there is an increase in the percentage of NK cell numbers in the peripheral blood. Decreased cell margination caused by catecholamines is the suggested mechanism.The lytic activity of the NK cells is also enhanced with a 40% increase in the NK cell activity one hour after exercise. However, sustained exercise shows a trend in favour of suppression of the NK cell activity. A study in 1995, has demonstrated a marked fall both in the number as well as the activity of the NK cells for almost a week following a single bout of 90-120 min of exercise at 65% of max heartrate. Endorphin induced inhibition and a late surge in the cortisol may be the contributory factors.
Immunoglobulins are produced by the plasma cells and are of different types: IgG, IgM, IgA, IgD and IgE. Of these, IgG is the most important and possesses antibacterial, antiviral as well as antitoxic antibodies along with opsonins to enhance phagocytosis. Most researchers have found that exhaustive exercise causes a decreased concentration of immunoglobulins in the serum, saliva, and the nasal secretions. There is also a corresponding decrease in their production lasting almost 4 days.
Soluble factors of the immune system C-reactive protein (CRP), interleukins and interferons. An acute bout of severe exercise elevates CRP which in turn activates the complement system which then reacts with antibodies to form opsonins. These opsonins are responsible for the phagocytosis by the macrophages. The interleukins are responsible for producing antibodies from the B cells and also for activation of the macrophages, T cells and NK cells.IL1 levels are increased during and following endurance exercise, while the IL2 levels fall immediately after strenuous exercise but rise after 24 hour following exercise. The interferons are produced by activated T lymphocytes. Plasma ?-interferon is increased following exhaustive exercise possibly because of muscle injury stimulating interferon release.
Glutamine is a key metabolic substrate for the immune system. It acts as a precursor for nucleotide biosynthesis and a major source of energy. Glucose synthetase is the major enzyme of glutamine synthesis and is found largely in the skeletal muscle but also in the lungs, the brain and certain other tissues in small amounts. Glutamine utilization is high in the muscles and the gastrointestinal tract. Deficiency of glutamine leads to impairment of immunity and thus an increase in the susceptibility to infection.
Athletes have been shown to have elevated levels of glutamine which may represent a positive adaptation to a well designed and graded training program. However, a number of studies have suggested low levels in athletes with over training. This may well be due to detrimental effect of excess stress of overtraining or shifting of balance in the favour of increased utilisation rather than synthesis of glutamine.
Physiology of the response to exercise
It has been suggested that exercise causes a response similar to an immune reaction, albeit of a smaller degree as compared to sepsis. This has been postulated from increased plasma levels of the markers of exercise. These are: infiltration by cells of the immune system like neutrophils within a few minutes of initiation of exercise and macrophages which follow subsequently. Activation of these cells follows with a resultant release of acute phase reactants and proinflammatory cytokines like IL-1, IL-6 and TNF-?. The net effect of all these processes is that there is stimulation of the complement, coagulation and the fibrinolytic system. Also, there is suppression of the circulating levels of NK cells as well as the NK cell activity to up to seven days. The leucocytes displayed a gradual but definite increase in their propensity for apoptosis during and following exercise. This was shown by TC Tuan et al by showing a causal relationship between mitochondrial transmembrane potential and raised pro-inflammatory mediators.
Studies have been conducted in the hope that the alteration in the immune parameters from a resting state can be used to know when an athlete is getting overtrained. This might allow athletes to train to the optimum without risking overstretching themselves and thus affecting performance. However, it is difficult to simulate overtraining in an individual because ethically an athlete cannot be asked to push himself/herself to the limits of causing injury. In a study carried out in 1992, distance runners, were already training hard were deliberately asked to train harder by 38% for 3 weeks. It was observed that the resting mitogen induced lymphocyte proliferation increased. Also, the helper to suppressor cell ratio and the mitogen induced synthesis of immunoglobulins decreased.
Moreover, the 30 min. of sub-maximal exercise now induced 18% suppression of lymphocyte proliferation and the exercise induced synthesis of immunoglobulins never occurred. However, most of these findings were too variable to be of any consequence. Similarly in a study conducted in 1995, most of the plasma biochemical concentrations associated with exercise were found to be within normal range. Thus, the so called markers of exercise cannot be, as yet, associated with the symptoms of overtraining syndrome or an increased susceptibility to infection during intense training. The only parameter showing significant deviation from the normal in response to exercise was found to be glutamine. However, a definite correlation between reduced levels of glutamine and clinical manifestations of overtraining or the underlying mechanisms are yet to be determined.
Better tests for measuring the plasma levels of immune cells and their actions, cytokines, glutamine, catecholamines, hypothalamic pituitary axis function and getting athletes to exercise more rigorously in the presence of environmental, nutritional or psychological stress to cause a greater degree of immune response may be more forthcoming to prove the association. At the moment, psychological testing probably provides a simpler and better way of detecting overtraining in an athlete.
Thus, whereas moderate exercise is beneficial to human health and immune system, rigorous exercise for prolonged periods can be detrimental. Hence, there is a need to know the optimum level of exercise to derive maximum benefit without compromising the benefits by pushing too hard.