Table 1 Relevant studies about the influence of psychological stress on the immune system

Ortega M. 2006 [90]

Stress is a risk factor for health in all systems of the body; even though a certain level of stress is essential to boost productivity, once a limit is exceeded by an intense stressor, the body becomes depleted, causing stress-associated diseases.

Rosenthal S. 2002 [91]

Ray O. 2004 [92]

Sierra R et al. 2006 [93]

Sandín B. 2008 [94]

McEwen B.S. 2008 [95]

An altered immune system caused by stressful events increases the body’s vulnerability (to infectious diseases, cancer and autoimmune diseases).

Borysenko J, Borysenko M. 1983 [96]

Gidron Y et al. 2003 [97]

Ho W, Evans D, Douglas S. 2002 [98]

Social, physical, and biological factors that cause stress may induce immunosuppression, including inability to adapt to the environment, trauma, major surgical interventions, radiation, infection, and cancer.

Monjan A, Collector M. 1977 [99]

Exposure to chronic stress induced proliferation of T and B lymphocytes similar to or to an even greater than a control treatment. Additionally, exposure of mice to acute noise stress for more than 2 to 3 h a day for fewer than 2 consecutive days reduced B and T lymphocyte proliferation in response to the mitogens lipopolysaccharide and concanavalin A, compared to non-exposure to stress.

Fillion L et al. 1994 [100]

Weiss J et al. 1989 [101]

Hucklebridge F, Clow A, Evans P. 1998 [102]

Stress is related to increased viral retention in tissues, along with a decrease in the number of circulating lymphocytes and in the mitogenic response in vitro. In addition, stress diminishes the activity of natural killer (NK) cells, a powerful mechanism for the elimination of tumor cells and the production of interferon-γ.

Moynihan J, Ader R, Crota L et al. 1990 [103]

Most immune responses are suppressed by stress, but moderately intense stress conditions can increase them.

Croset G et al. 1987 [104]

Rat immune system reactivity was tested by determining the proliferative response after mitogenic stimulation in vitro as well as the capacity to generate a primary antibody response after immunization with red blood cells from sheep. An increase in the immune response in vitro and in vivo was demonstrated following exposure to a single shock. Thus, it was concluded that emotional stimuli facilitate immune responses. However, when a rat was confronted with a conflict situation, there was a decrease in the reactivity of the immune system. These findings led to the final conclusion that the immune system specifically and immediately reacts to different psychological stimuli.

Shirinsky I, Shirinsky V. 2001 [105]

Belova T et al. 1988 [106]

Immune reaction initiation may be strongly affected by stress-induced cerebrovascular damage.

Churin A et al. 2003 [107]

Immobilization stress induces different immune system reactions in distinct strains of rodents. These reactions can be classified according to the intensity of the humoral immune response for thymus-dependent antigens into categories such as high, moderate and low responders. High and moderate responders are characterized by high sensitivity of the productive phase of the humoral immune response and the phagocytic activity of macrophages. In low responders, stress only slightly affected the productive phase of the humoral immune response, but peritoneal macrophage activity decreased. This evidence reflects the different reactions of the immune system.

De Groot J et al. 2002 [108]

This study of stress revealed the consequences of stress on the quality and quantity of immunological memory in the long term. Mice were subjected to social stress after herpes simplex virus infection. Stressed mice were shown to exhibit suppressed antibody response and impaired memory for the production of IL4 and IL10 as a specific response to the virus, whereas non-stressed mice showed intact immune responses and immune memory.

Guayerbas N et al. 2002 [109]

This study found that on standard behavioral tests, rodents with high levels of anxiety had less competition in their immune system (premature immunosenescence), as demonstrated by certain functional alterations of peritoneal macrophages, such as substrate adherence, chemotaxis, phagocytosis, and superoxide anion production.

Zelena D et al. 2003 [110]

In rats subjected to stress by repeated trapping, chronic stress signs including decreased thymus size and weight, increased adrenal gland weight, and increased basal corticosterone levels were observed.

Molina P. 2001 [111]

Studies in rats subjected to hemorrhagic shock stress showed a suppressive role of noradrenergic innervation in the increase in tissue TNF-α levels initiated by hemorrhage in vivo. Therefore, it was concluded that norepinephrine protects against tissue damage but may contribute to generalized immunosuppression following trauma.

Wonnacott K, Bonneau R. 2002 [112]

In a murine model, stress reduced the ability of specific cytotoxic memory T lymphocytes to protect against lethal intranasal or intravaginal infection with a herpes simplex virus. Stress also restricted the ability of these lymphocytes to limit virus levels at the site of the infected mucosa.

Paltrinieri S et al. 2002 [113]

The efficiency of granulocytes was studied in sheep subjected to acute stress, and the results demonstrated that acute stress significantly increased the adhesion of these cells. This mechanism could be responsible for the depression of innate immunity observed in stressed animals.

Sánchez M, Cruz C. 1991 [114]

Human studies revealed that IgA class antibodies, which are important in the defense against viruses and bacteria, had reduced abundance in individuals with a particular personality type.

Stowell J. 2003 [115]

In humans, certain academic examinations can have a noteworthy impact on mental and physical health.

Matalka K. 2003 [116]

A review of mental stress models (short and written examinations as subacute and acute types of stressors) was conducted to understand the effects of stress on the neuroendocrine and immune systems. In stressed students, a short period (minutes) of preparation for a written exam induced the production of proinflammatory cytokines, which could be related to a Th1 response. Nevertheless, prolonged mental stress (of several days) caused deregulation of immune function, with a change in the cytokine response to a Th2 response.

Anyanwu E et al. 2003 [117]

Abnormal NK cell activity was found in patients exposed to toxigenic materials, leading to adverse health conditions, including a wide range of neuroimmune and behavioral consequences.

Ho C et al. 2001 [118]

Measurable changes in dendritic cell abundance were observed in patients undergoing surgery. These cells were rapidly mobilized in the circulation in response to surgical stress, and this activity may prepare host immune defenses against trauma.

Woiciechowsky C et al. 1998 [119]

In patients with sympathetic activation due to acute accidental brain trauma, rapid systemic release of the anti-inflammatory cytokine IL10 from non-stimulated monocytes occurs. The rapid release of this cytokine may signify a common pathway for stress-induced immunosuppression.

Dhabhar F, McEwen B. 1999 [120]

Divergent from the concept that stress impairs immunity, human studies showed that short-term stressors pointedly increase delayed hypersensitivity reactions of skin.

Glaser R. 2005 [121]

Individuals exposed to chronic diseases are more likely to present deleterious health and hygiene habits compared to individuals who do not have stress, such as sleep disturbances, malnutrition, physical inactivity and drug and tobacco abuse; thus enhancing the adverse effects of stress on the immune system and overall health.

Levitina E. 2001 [122]

Immunological studies in infants who suffered from perinatal hypoxic stress demonstrated impaired cellular immunity (lymphocyte subpopulations) and humoral immunity (immunoglobulin concentrations). Acute hypoxia led to transient immunodeficiency due to stress.

Ramos, V et al. 2008 [123]

Chronic and excessive stimulation of the hypothalamic-pituitary-adrenal axis induces the production of glucocorticoids, the final products of this axis, altering the levels of white blood cells, decreasing the activity of NK cells and inhibiting the production and secretion of ILs that are important in mediating the immune response.

Mohr D, Pelletier D. 2004 [124]

Stress in individuals with multiple sclerosis increases the permeability of the blood–brain barrier to immune cells circulating in the blood. As a result, there is an increase in the infiltration of leukocytes into the CNS.

Selye H. 1936 [125]

Hypotrophy of the thymus and lymph nodes was demonstrated after exposure to stress. The immunomodulatory effect of glucocorticoids is essential to this effect.

Kay G et al. 1998 [126]

Prenatal stress from maternal isolation and exposure to noise and intense light during the last week of gestation in rats reduced the proliferative response of B lymphocytes and decreased the cytotoxic activity of NK cells in peripheral blood.

Spitzer et al. 2010 [127]

People diagnosed with post-traumatic stress disorder were found to be significantly more likely to have elevated C-reactive protein levels.

Gill J, Page G 2008 [128]

Gola et al. 2013 [129]

Sutherland, A., Alexander, D. Hutchison, J.2003 [130]

von Kanel et al. 2006 [131]

von Kanel et al. 2007 [132]

Baker et al. 2001 [133]

Maes et al. 1999 [134]

Newport D, Nemeroff C. 2000 [135]

Research showed that people with post-traumatic stress disorder have elevated levels of proinflammatory cytokines, especially IL6, which has been considered a potential prognostic biomarker for this pathology.

Gotovac et al. 2010 [136]

Pace et al. 2012 [137]

Evidence was found for cytotoxic changes to NK cells in people with post-traumatic stress disorder, as well as an increase in the number of glucocorticoid receptors on lymphocytes and a decrease in the sensitivity to glucocorticoids.

Cohen et al. 2001 [138]

Herbert T, Cohen S. 1993 [139]

Reduced NK cell cytotoxicity, suppressed lymphocyte proliferative responses, and blunted humoral responses to immunization were found in chronic stress models.

Montoro J et al. 2009 [140]

Activation of the neuroendocrine and sympathetic nervous systems through catecholamine and cortisol secretion influences the immune system, modifying the balance between Th1 and Th2 responses in favor of the Th2 response.