McEwen (1998). Protective and damaging effects of stress mediators – Article summary

Allostatic load refers to the long-term effect of the physiological response to stress. Allostasis refers to the ability to achieve stability through change. The nervous system, the HPA axis, the immune system and other systems protect the body through allostasis.

The effects of chronic stress can be exacerbated by a rich diet (1), the use of tobacco (2) and the use of alcohol (3). It can be reduced by moderate exercise. The way a person perceives the situation and a person’s general state of physical health determine individual responses to potentially stressful situations. The ability to adjust or habituate to repeated stress is influenced by the way a person perceives the situation.

Chronic stress refers to feelings of fatigue, lack of energy, irritability, demoralization and hostility. This is a risk factor for the development non-insulin dependent diabetes. Deposition of abdominal fat is increased by psychosocial stress.

Allostatic systems enable us to respond to our physical states and to cope with noise, crowding, isolation, hunger, extremes of temperature, danger and microbial and parasitic infection. The body’s response to a challenge is turning on an allostatic response and turning it off when the threat is past. The most common allostatic responses involve the sympathetic nervous system and the HPA axis.

Activation of the sympathetic nervous system and the HPA axis leads to the release of catecholamines from nerves and the adrenal medulla. This leads to the secretion of corticotropin from the pituitary. The corticotropin mediates the release of cortisol from the adrenal cortex. Inactivation returns the system to baseline levels of cortisol and catecholamine secretion.

However, if inactivation is inefficient, there is overexposure to stress hormones. This can result in allostatic load. There are four types of allostatic load:

• Frequent stress
• Prolonged exposure to stress hormones as a result of a lacking adaptation to repeated stressors of the same type (e.g. public speaking remains stressful even after a long time).
• Inability to shut off allostatic responses after stress is terminated
• Compensatory increases in other systems as a result of inadequate responses in by some allostatic systems (e.g. more cytokine secretion if cortisol secretion does not increase with stress).

The negative feedback effects of cortisol are reduced in elderly humans, meaning that the cortisol secretion levels take longer to return to baseline levels after activation if a person is older. This may be because allostatic load over a lifetime causes the allostatic systems to become exhausted. The glucocorticoidcascade hypothesis states that wear and tear of the hippocampal region leads to dysregulation of the HPA axis and cognitive impairment.

Feelings of anticipation and worry can increase allostatic load. Anticipatory anxiety can drive the secretion of mediators (e.g. corticotropin) and prolonged anxiety thus contributes to allostatic load. Allostasis and allostatic load are also affected by the consumption of tobacco and alcohol, dietary choices and the amount of exercise.

A lack of control on the job increases risk of coronary heart disease. Job strain results in elevated ambulatory blood pressure at home, an increased left-ventricular-mass index and increased progression of atherosclerosis. Chronic stress and hostility are linked to increased reactivity in the fibrinogen system and of platelets, which increases the risk of myocardial infarction.

Repeated stress affects brain function, especially in the hippocampus. Impairment of the hippocampus decreases the reliability and accuracy of contextual memories, which may exacerbate stress by preventing access to the information needed to decide that a situation is not a threat. The hippocampus also regulates the stress response and inhibits the response of the HPA axis to stress.

Acute stress increases cortisol secretion which suppresses the mechanisms in the hippocampus and temporal lobe that serve the short-term memory. This means that stress can affect memory but these effects are short-lived and reversible. Repeated stress causes atrophy of dendrites of pyramidal neurons in the CA3 region of the hippocampus .

Aging of the brain may be accelerated due to stress but this is not sure yet. Isolation and a lack of control in the work environment are related to increases in allostatic load.              

The immune-enhancing effects of acute stress depend on adrenal secretion and last for three to five days. Acute stress prepares the immune system for immediate threat. This form of allostasis enhances responses for which there is an established immunologic memory. If the immunologic memory is of a tumour cell, the action is beneficial. However, if the immunologic memory is of an allergic response, the activation is maladaptive.

The hypersensitivity response of the immune system is substantially inhibited rather than enhanced when allostatic load is increased by repeated stress. This leads to suppressed cellular immunity (e.g. leading to more severe forms of the common cold).