alternative and complementary medicine stress and immunity
  Stress and Immunity
From   Lewis Mehl-Madrona, M.D., Ph.D.


Stress and Immunity

The experience of stress affects cellular immunity, an important aspect of many medical problems, including controlling/curing cancer and the immunobiology of autism. Treating disease with immunological components means also treating and managing psychological stress.

Human immune function is mediated by the release of cytokines, nonantibody messenger molecules, from a variety of cells of the immune system, and from other cells, such as endothelial cells. There are Th1 and Th2 cytokines. Autoimmune and allergic diseases involve a shift in the balance of cytokines toward Th2. The autoimmune aspect of autism has been related to excessive Th2 cytokines resulting, in part, from vaccination. Gulf War syndrome and asthma have been similarly linked to excess immunization in the presence of increased environmental toxins and pollutants (high antigenic load).

Cytokines stimulate cellular release of specific compounds involved in the inflammatory response. Stress-induced activation of the sympathetic nervous system and the sympathetic-adrenal medullary and hypothalamic-pituitary adrenal axes lead to the release of cytokines 1. Blocking the response of the sympathetic nervous system by pre-treating subjects in stressful experiments with adrenergic antagonists can reduce this release of cytokines and decrease the resulting inflammatory response 2, 3. Discrete areas of the brain (for example, the hypothalamus and the locus coeruleus) regulate the sympathetic nervous system and therefore the levels of circulating adrenergic stress hormones, thereby influencing the activity of the immune system 4, 5. Adrenergic stress hormones alter the synthesis and release of cytokines by white blood cells (leukocytes).

The effects of stress on immunity has been experimentally studied in animals. The stress of crowding prior to and following tuberculosis infection affects the outcome of the infection in mice 6. Social disruption in mice causes reactivation of latent herpes simplex virus 7. Stress enhances the reactivation of latent herpes viruses including the Epstein-Barr virus in humans 8.

Psychological stress inhibits many aspects of the immune response including innate immunity (eg, natural killer cell lysis), T-cell responses, and antibody production [1]. Caregivers of parents with Alzheimers disease along with matched noncaregivers received influenza vaccine. All subjects had similar vaccine histories, rates of chronic illnesses, and medication usage, but caregivers showed poorer cellular and humoral immune responses to the vaccine than controls 9 - 12. Their less robust response was thought to relate to the chronic stress of caregiving.

Acute stress can suppress the virus-specific antibody and T-cell responses to hepatitis B vaccine 2, 13-15. People who show poorer responses to vaccines have higher rates of clinical illness including influenza virus infections 16, so these findings are clinically relevent.

Stress influences host resistance to upper respiratory tract infections produced by exposure to five different strains of rhinovirus, to a strain of coronavirus, and to respiratory syncytial virus. After inoculation, subjects were quarantined and monitored for 5 or more days to assess whether they developed infections and cold symptoms. Approximately one third of those subjects exposed to one of these viruses developed a serologically verified clinical illness 17. Higher scores on a questionnaire for stressful life events, higher perceptions of stress, and more negative emotional experiences were associated with a greater likelihood of developing a clinical illness defined as cold symptoms concomitant with isolating an infectious virus or developing a 4-fold increase in antibody titers 18.

In a second study, a life-stress interview replaced the questionnaire. This technique allowed the specification of the types of stressful events that increase risk. These included chronic events (lasting a month or longer), especially chronic social conflicts and underemployment or unemployment 18. Other plausible factors that might be the cause of both changes in stress and greater susceptibility to disease, such as age, sex, education, and personality characteristics including self-esteem and personal control, were unable to account for these results. The results demonstrated a relationship between psychological stress and susceptibility to several cold viruses.

Attempts to find an association between stress and disease progression in patients with acquired immunodeficiency syndrome (AIDS) have met with conflicting results 19. Among a cohort of San Francisco AIDS patients, depression predicted CD4+ T-lymphocyte decline 20 and mortality 21. Analysis of the Multicenter AIDS Cohort Study failed to observe an association between depression and the decline of CD4+ T lymphocytes, disease progression, or death 22, but others have found significant associations between immunological parameters reflective of HIV progression and psychosocial factors, particularly denial and distress 23 and concealment of homosexual identity 24.

Outside of proven clinical interventions, there is reason to think that certain changes in lifestyle might increase host resistance to infectious diseases. These include broadening one's social involvements (eg, joining social or spiritual groups, having a confidant, spending time with supportive friends) and being more careful to maintain healthful practices such as proper diet, exercise, and sleep, especially under stressful conditions 26.


REFERENCES

1. Rabin BS. Stress, Immune Function, and Health: The Connection. New York, NY: Wiley-Liss & Sons Inc; 1999.

2. Bachen EA, Manuck SB, Cohen S, et al. Adrenergic blockade ameliorates cellular immune responses to mental stress in humans. Psychosom Med. 1995;57:366-372. MEDLINE

3. Benschop RJ, Nieuwenhuis EES, Tromp EAM, Godaert GLR, Ballieux RE, van Doornen LJP. Effects of beta-adrenergic blockade on immunologic and cardiovascular changes induced by mental stress. Circulation. 1994;89:762-769. MEDLINE

4. Wetmore L, Nance DM. Differential and sex-specific effects of kainic acid and domoic acid lesions in the lateral septal area of rats on immune function and body weight regulation. Exp Neurol. 1991;113:226-236. MEDLINE

5. Rassnick S, Sved AF, Rabin BS. Locus coeruleus stimulation by corticotropin-releasing hormone suppresses in vitro cellular immune responses. J Neurosci. 1994;14:6033-6040. MEDLINE

6. Tobach E, Bloch H. Effect of stress by crowding prior to and following tuberculosis infection. Am J Physiol. 1956;187:399-402.

7. Padgett DA, Sheridan JF, Dorne J, Berntson GG, Candelora J, Glaser R. Social stress and the reactivation of latent herpes simplex virus-type 1. Proc Natl Acad Sci U S A. 1998;9:7231-7235.

8. Glaser R, Kiecolt-Glaser JK. Stress-associated immune modulation and its implications for reactivation of latent herpesviruses. In: Glaser R, Jones J, eds. Human Herpesvirus Infections. New York, NY: Marcel Dekker Inc; 1994:245-270.

9. Kiecolt-Glaser JK, Glaser R, Gravenstein S, Malarkey WB, Sheridan J. Chronic stress alters the immune response to influenza virus vaccine in older adults. Proc Natl Acad Sci U S A. 1996;93:3043-3047. MEDLINE

10. Kiecolt-Glaser JK, Marucha PT, Malarkey WB, Mercado AM, Glaser R. Slowing of wound healing by psychological stress. Lancet. 1995;346:1194-1196. MEDLINE

11. Kiecolt-Glaser JK, Page GG, Marucha PT, MacCallum RC, Glaser R. Psychological influences on surgical recovery: perspectives from psychoneuroimmunology. Am Psychol. 1998;53:1209-1218. MEDLINE

12. Vedhara K, Cox NKM, Wilcock GK, et al. Chronic stress in elderly caregivers of dementia patients and antibody response to influenza vaccination. Lancet.1999;353:627-631. MEDLINE

13. Glaser R, Kiecolt-Glaser JK, Bonneau RH, Malarkey WB, Kennedy S, Hughes J. Stress-induced modulation of the immune response to recombinant hepatitis B vaccine. Psychosom Med 1992;54:22-29. MEDLINE

14. Jabaaij L, Grosheide RA, Heijtink RA, Duivenvoorden HJ, Ballieux RE, Vingerhoets AJ. Influence of perceived psychological stress and distress antibody response to low dose rDNA hepatitis B vaccine. J Psychosom Res. 1993;37:361-369. MEDLINE

15. Glaser R, Kiecolt-Glaser JK, Malarkey WB, Sheridan JF. The influence of psychological stress on the immune response to vaccines. Ann N Y Acad Sci. 1998;840:649-655. MEDLINE

16. Gravenstein S, Drinka P, Duthie EH, et al. Efficacy of an influenza hemagglutinin-diphtheria toxoid conjugate vaccine in elderly nursing home subjects during an influenza outbreak. J Am Geriatr Soc. 1994;42:245-251. MEDLINE

17. Cohen S, Tyrrell DAJ, Smith AP. Psychological stress in humans and susceptibility to the common cold. N Engl J Med. 1991;325:606-612. MEDLINE

18. Cohen S, Frank E, Doyle WJ, Skoner DP, Rabin BS, Gwaltney Jr JM. Types of stressors that increase susceptibility to the common cold in adults. Health Psychol. 1998;17:214-223. MEDLINE <

19. Solomon GF, Kemeny ME, Temoshok LT. Psychoneuroimmunologic aspects of human immunodeficiency virus infection. In: Ader R, Felten D, Cohen N, eds. Psychoneuroimmunology. San Diego, Calif: Academic Press; 1991:1081-1114.

20. Burack JH, Barrett DC, Stall RD, Chesney MA, Ekstrand ML, Coates TC. Depressive symptoms and CD4 lymphocyte decline among HIV-infected men. JAMA. 1993;270:2568-2573. MEDLINE

21. Mayne TJ, Vittinghoff E, Chesney MA, Barrett DC, Coates TJ. Depressive affect and survival among gay and bisexual men infected with HIV. Arch Intern Med. 1996;156:2233-2238. MEDLINE

22. Lyketsos CG, Hoover DR, Guccione M, et al. Depressive symptoms as predictors of medical outcomes in HIV infection. JAMA. 1993;270:2563-2567. MEDLINE

23. Ironson G, Friedman A, Klimas N, et al. Distress, denial and low adherence to behavioral interventions predict faster disease progression in gay men infected with human immunodeficiency virus. Int J Behav Med. 1994;1:90-105.

24. Cole S, Kemeny M, Taylor S, Visscher B, Fahey J. Accelerated course of HIV infection in gay men who conceal their homosexuality. Psychosom Med. 1996;58:219-231. MEDLINE

25. Herbert TB, Cohen S. Stress and immunity in humans: a meta-analytic review. Psychosom Med. 1993;55:364-379. MEDLINE

26. Cohen S, Doyle WJ, Skoner DP, Rabin BS, Gwaltney Jr JM. Social ties and susceptibility to the common cold. JAMA.1997;277:1940-1944.


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