Stress can either enhance or suppress immune functions, depending on a variety of factors such as duration of a stressful condition. While acute stress can have immune benefits, chronic stress (distress) has been demonstrated to exert a significant suppressive effect on immune function (1) and gradual degradation of the immune system. This results in a range of illnesses including cancer, and increasing vulnerability to viruses, from herpes to the common cold.
Impaired immune response
As early as 1977, studies showed that immunosuppression, measured by a drop in proliferation of lymphocytes (a type of white blood cell in the immune system), occurred to a significant extent among people who were mourning the loss of a loved one (2,3), and that the number of lymphocytes in medical students dropped significantly during stressful periods such as exams (4).
Stress has been shown to: decrease the number of leukocytes; impair immune response to immunisations; affect T-cell response and antibody production; and diminish cytotoxity of natural killer (NK) cells, the rapid response to viruses and cancer cells (5,6,7).
An extensive body of experimental and clinical evidence documents the negative impact of chronic psychological stress and depression on the immune system and health. One study found that stress, and stress-related depression, could result in a lowering of lymphocyte activity (including NK cells) by up to 50%. The significant finding of this study, however, was that this diminished lymphocyte activity could be prevented to a large extent by a diet high in antioxidants (8). Natural killer (NK) cell impairment is associated with the increased likelihood of contracting infectious diseases, susceptibility to autoimmune diseases and cancer (9).
Interpersonal stress impacts most
Research also suggests that interpersonal stressors, especially chronic ones, appear to produce a greater change in immune function than non-social stressors (10). In a study of rats, the dominance or status of male rats was often linked to their immunological outcome (11). The subdominant rats (a bit like low status employees) experienced induced fear states, which were linked to an increase in secretion of catecholamines (11). Furthermore, the immunological status of the unchallenged winner or dominant male rat caused a restoration of the original immunological status, but this is not observed for the "loser" or subdominant rats. Mammalian immune suppression is associated with the following changes: impaired neutrophil phagocytosis; increased neutophil (most abundant type of white blood cells) and lymphocyte populations (12).
While it is believed that a number of stress-related hormones may be responsible for various aspects of immunological suppression, both glucocorticoid and catecholamine hormones released in stress situations are associated with a role as an immunosuppressant (13).
Research currently suggests that it is cortisol that plays the most damaging role, by reducing both the prevalence and activity levels of T-cells (14). One study examined the effects that a stressful external factor can have on sleep by measuring the serum cortisol levels of 40 brewery workers exposed to high levels of industrial noise (>85dBA) and who also had various medical problems including insomnia (55%), migraine (50%), and irritability (27.5%) (15). Despite wearing the correct hearing protection, those exposed to industrial noise had much higher cortisol levels at the end of the day than did a control group working in a quiet section of the brewery (15).
Extended exposure to cortisol impacts your lymphocyte and eosinophil cell counts (16). Lymphocytes represent a variety of white blood cells located within your body, present in your blood, bone marrow, gut walls and spleen. Lymphocytes produce antibodies and T lymphocytes, which are responsible for cellmediate immunity. Lymphocytes are dynamic as they can change into regeneration cells or kill other foreign cells within the body, such as viruses (17). Eosinophil cells mainly combat viral infections; an increase in eosinophil cells may indicate a virus present within the body (17).
More susceptible to infections
The role of stress as an immunosuppressant is currently widely accepted. An increase in vulnerability to the pathogenesis of disease in chronically affected individuals (18) and other studies have consistently found higher levels of psychological stress show a greater susceptibility to infectious disease. People with higher rates of stress were significantly more likely to contract respiratory infections than those who lead comparatively "stress free" lives (19). Similarly other research has shown that the reactivation of latent herpes viruses was significantly enhanced in individuals under stress (20). One study showed that subjects reporting a higher level of stress exhibited poorer antibody responses to the influenza vaccine, increasing the likelihood of infection (21).
Up to two thirds of the population have an ulcer-causing bacteria already in their stomachs, but only a small proportion of people, more frequently people with higher stress levels, actually have stomach ulcers (22,23).
We are exposed to many possible infections every day, including meningococcal bacteria in up to 30% of the population, but only a very small percentage of the population contract the illness. Meningococcal septicemia was known as the "partiers' disease" because it was associated with 18 to 25 year olds who were very socially active.
Many of us are also more vulnerable to catching the flu when we are chronically stressed. Chronic stress and depression may also contribute to dental problems, in particular pathogenic infection and concomitant periodontal tissue destruction (24).
Stress has also been shown to slow healing. A metaanalysis found 17 out of the 22 studies investigated showed stress was associated with impaired wound healing or the disregulation of a biomarker associated with wound healing (25). In support of this, a preliminary study found caregivers with a higher reported stress rate had a slower rate of wound healing than non-caregivers, with no other health related differences that could influence the study (26).
Psychological stress is a public health issue, even in children, and has been associated with a number of immunological diseases. Emerging work in the field of health psychology suggests that early life stress also impacts physical wellbeing. One study found that children living in high stress households are more vulnerable to lung damage from traffic pollution than children whose parents are less "stressed out" (27). In the study of nearly 1,400 children living in southern California, kids from high stress homes had an approximate 5% reduction in lung function compared to controls. An earlier study by some of the same researchers found that children exposed to traffic related air pollution and a high stress home were 51% more likely to develop asthma than children exposed to the same pollutants, but in a low stress environment (27).
Children from families with high psychological stress showed low spontaneous immune activity but an increased immune response in other areas. Children within the high stress group showed high levels of cortisol, but low levels of C-peptide (28). In another study, those who experienced severe early life stress as children were found to be more at risk for cardiovascular disease, type 2 diabetes, and cancer compared with those who did not have those early life experiences; this is probably due to increased inflammation (29).
The effects of prenatal maternal stress (PNMS) on the developing immune system have also been demonstrated. PNMS is a relevant factor in the programming of immune function, with consequences related to disorders with an important immune component such as allergies (30).
Stress and Cancer
The persistent activation of the chronic stress response, and the response to chronic depression, impairs the immune response and is implicated in the development and progression of some types of cancer (31). In a study of 516 colorectal patients and the levels of stress they had suffered in the 10 years prior to the development of cancer, the higher levels of stress were found to increase the risk of colorectal cancer by 5½ times. That is 550%.
A case-controlled study of 257 women with breast cancer revealed that, after adjustments for age and confounding factors, women with major life events, stress of daily activity and depression had a 3.7 times (370%) higher risk for breast cancer, in comparison to those who did not experience such stressors (32).
Researchers examined information from 989 women who had been diagnosed with breast cancer, and found that the women with the most stress were most likely to have aggressive forms of breast cancer. In particular, women under significant stress were 38% more likely to have estrogen receptor-negative cancers, or cancers that don't respond to some of the more common therapies that cut off estrogen supply. Also, the women with higher stress levels were more likely to have high grade (more aggressive) tumors. In support of this, another study found that breast cancer patients with the most anxiety had the lowest level of natural killer cells, part of the defense system to protect against cancer and infection. Women with higher levels of stress had 20% to 30% fewer natural killer cells. In another study, chronic stress was found to increase inflammation, which increased dilation of lymphatic collector vessels to promote breast cancer metastasis (spread) (33).
In animal studies, social isolation is a potent psychosocial stressor and is associated with increased breast cancer risk and mortality. The formation of mammary tumors was significantly higher in socially isolated mice (34).
In a meta-analysis of 165 studies, researchers found that stress-related psychosocial factors were associated with higher cancer incidence in initially healthy populations; in addition, poorer survival in patients with diagnosed cancer was noted in 33 studies, and higher cancer mortality was seen in 53 studies (35).
Stress-prone personality, unfavourable coping styles, negative emotional responses or poor quality of life were related to higher cancer incidence, poorer cancer survival and higher cancer mortality. Site-specific analyses indicate that psychosocial factors are associated with a higher incidence of lung cancer and poorer survival in patients with breast, lung, head and neck, hepatobiliary, and lymphoid or hematopoietic (blood formation) cancers (35). Head and neck cancer have also been associated with posttraumatic stress disorder (36).
In mice, stress-induced neural activation increased primary tumor growth and tumor cell dissemination to normal adjacent pancreas. These effects were associated with increased expression of invasion genes by tumor cells and pancreatic stromal cells for beta-adrenergic signaling (37).
The overwhelming body of information now clearly shows that stress has a major impact on the immune system and the development of chronic disease such as cancer. The next step is to ask yourself what can you do to reduce your stress?
DISCLAIMER: Dr Peter Dingle is a researcher, educator and public health advocate. He has a PhD in the field of environmental toxicology and is not a medical doctor.
References:Dan Hu et al. 2014Shleifer et al. 1983; Bartrop et al. 1977Kiecolt-Glaser et al. 1984Anderson et al. 1998; Rabin 1999; Wooten 1996). Blake-Mortimer et al. 1996Cohen et al. 2007Herbert and Cohen 1993Stefanski 2001Song and Leonard 1995Juster, McEwan and Lupien 2009Seaward 2002Gonzalez 2005Keller 1981Hania et al. 2007Leonard 2005Cohen et al. 1998Glaser and Kiecolt-Glaser 1994Miller and Cohen et al. 2004Wilyard 2009; Kwiecien 2007Warren et al. 2014Walburn et al. 2009Glaser 1995Islam et al. 2008Emma Carlsson et al. 2014Fagundes and WayFranz Veru et al. 2014Reiche et al. 2004Kruk and AboulEnein 2004Le et al. 2014Sumis 2014Chida et al. 2008Posluszny et al. 2014Kim-Fuchs et al. 2014
Dr Peter Dingle (PhD) has spent the past 30 years as a researcher, educator, author and advocate for a common sense approach to health and wellbeing. He has a PhD in the field of environmental toxicology and is not a medical doctor. He is Australia’s leading motivational health speaker and has 14 books in publication.