Since 1957 we know that stressful events in mice influence susceptibility to infection (Blog of March 2024). It took more than 20 years (1984) to show that a naturally occurring stressor in humans inhibits natural killer cell function.

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Kiecolt-Glaser JK, Garner W, Speicher C, Penn GM, Holliday J, Glaser R. Psychosocial modifiers of immunocompetence in medical students. Psychosom Med. 1984;46:7-14. doi: 10.1097/00006842-198401000-00003. PMID: 6701256

The authors

Prof. Janice Kiecolt-Glaser (1940s-) is a clinical psychologist working in the field of psychoneuroimmunology. She completed her undergraduate degree in psychology at the University of Oklahoma. She went on to complete her PhD in psychology at the University of Miami in 1974. From here, she went to the hotspot of 1970 psychoneuroimmunology, which was Rochester, New York, to continue as post-Doc. At the beginning of the 1980s she moved to Columbus, Ohio, to work together with Ronald Glaser, and both together were co-founders of the field PsychoNeuroImmunology. Today, Janice Kiecolt-Glaser is S. Robert Davis Chair of Medicine and Distinguished University Professor at the Ohio State University College of Medicine. She is a clinical health psychologist specializing in psychoneuroimmunology and Director of the Ohio State Institute for Behavioral Medicine Research.

Ronald Glaser (1939-2019), her husband, received a Bachelor of Arts in biology in 1962 from the University of Bridgeport, Connecticut. In 1964 he was awarded a Master of Arts in physiology from the University of Rhode Island in Kingston. He earned a doctoral degree in virology from the University of Connecticut, Storrs. From 1968 through 1969, Dr. Glaser was a postdoctoral fellow at the Baylor College of Medicine in Houston, Texas. He joined the faculty at the Pennsylvania State University College of Medicine in Hershey, Pennsylvania, as an assistant professor in 1970. He rose through the academic ranks, becoming a full professor in 1977. Dr. Glaser was recruited to Ohio State in 1978 to chair the department of medical microbiology and immunology in the College of Medicine. In 1996, Dr. Glaser became the founding director of the Institute for Behavioral Medicine Research (IBMR) in the College of Medicine, where he stayed until his retirement.

The starting point

Since the work of Rasmussen et al. (lit.1, and Blog of March 2024), it was known that stressful events in mice influence susceptibility to infection. Particularly in the 1970s, several more important studies showed the relationship between stressful events and changes in immune function (e.g., 2-3), which might even change susceptibility to tumor development (4,5). However, this work in animals needed to be translated in to science in humans. In order to do so, Janice Kiecolt-Glaser et al. studied the naturally occurring examination stress in medical students.

The discovery

In the critical work of Kiecolt-Glaser and Glaser (6), blood was drawn twice from 75 first-year medical students, with a baseline sample taken one month before their final examinations and a stress sample drawn on the first day of final examinations. Natural killer cell activity declined significantly from the first to the second sample (figure). High scorers on stressful life events and loneliness had significantly lower levels of natural killer cell activity (p<0.006  and p<0.02, respectively).

Discussion

The authors wrote:

Our data demonstrate the effects of a relatively minor stressor, final examinations, on an important component of the immune response, natural killer cell (NK) activity. We were also able to show that two variables thought to have an impact on illness, stressful live events and loneliness, did indeed have significant effects on NK activity. Any statement relating these variables and decreased NK cell function to malignant disease would be speculative, however, and will require more knowledge about the function of NK cells.

The important aspect of Kiecolt-Glaser’s work is the study subject, the human sufferer. In later work, she focused on loneliness, marital distress, caregiving, breast cancer survivors (fatigue and inflammation), nutrition and obesity, nutrition and marital status, nutrition and breast cancer survivorship, nutritional interventions (loneliness, aging, and inflammation), and Yoga and inflammation (7). According to Google Scholar, she has an h-index of 137 and a total of 83382 citations, which shows the impact of her exceptional work.

Neuroimmunomodulation also published papers on the link between stress in humans and immune function (8-16 and many more).

References

1. Rasmussen AF Jr, Marsh JT, Brill NQ. Increased susceptibility to herpes simplex in mice subjected to avoidance-learning stress or restraint. Proc Soc Exp Biol Med. 1957;96:183-189
2. Gisler RH: Stress and the hormonal regulation of the immune response in mice. Psychotherapy and Psychosomatics 1974;23:197-208
3. Monjan AA, Collector MI. Stress-induced modulation of the immune response. Science 1977;196:307-308
4. Riley V. Mouse mammary tumors: alteration of incidence as apparent function of stress. Science. 1975;189:465-467
5. Sklar LS, Anisman H. Stress and coping factors influence tumor growth. Science 1979;205:513-515
6. Kiecolt-Glaser JK, Garner W, Speicher C, Penn GM, Holliday J, Glaser R. Psychosocial modifiers of immunocompetence in medical students. Psychosom Med. 1984;46:7-14
7. Malarkey WB. Psychoneuroimmunology and the research of Janice Kiecolt-Glaser: It informs self-care and the practice of medicine. Comp. Psychoneuroendocrinology 2024;20:100260
8. Tringali G, Farrace S, Ragazzoni E, Dello Russo C, Piscitelli R, Preziosi P, Navarra P. Circulating interleukin-1-beta levels after acute and prolonged exposure to low temperatures: human and rat studies. Neuroimmunomodulation. 2000;7:177-181
9. Stowe RP, Pierson DL, Feeback DL, Barrett AD. Stress-induced reactivation of Epstein-Barr virus in astronauts. Neuroimmunomodulation. 2000;8:51-58
10. Gomez-Merino D, Drogou C, Chennaoui M, Tiollier E, Mathieu J, Guezennec CY. Effects of combined stress during intense training on cellular immunity, hormones and respiratory infections. Neuroimmunomodulation. 2005;12:164-172
11. Christian LM, Graham JE, Padgett DA, Glaser R, Kiecolt-Glaser JK. Stress and wound healing. Neuroimmunomodulation. 2006;13:337-346
12. Gouin JP, Hantsoo L, Kiecolt-Glaser JK. Immune dysregulation and chronic stress among older adults: a review. Neuroimmunomodulation. 2008;15:251-259
13. Arranz L, de Vicente A, Muñoz M, De la Fuente M. Impaired immune function in a homeless population with stress-related disorders. Neuroimmunomodulation. 2009;16:251-260
14. Dhabhar FS. Enhancing versus suppressive effects of stress on immune function: implications for immunoprotection and immunopathology. Neuroimmunomodulation. 2009;16:300-317
15. Jeckel CM, Lopes RP, Berleze MC, Luz C, Feix L, Argimon II, Stein LM, Bauer ME. Neuroendocrine and immunological correlates of chronic stress in ‘strictly healthy’ populations. Neuroimmunomodulation. 2010;17:9-18
16. Matos-Gomes N, Katsurayama M, Makimoto FH, Santana LL, Paredes-Garcia E, Becker MA, Dos-Santos MC. Psychological stress and its influence on salivary flow rate, total protein concentration and IgA, IgG and IgM titers. Neuroimmunomodulation. 2010;17:396-404

(Featured image declaration: modified from cookie_studio from Freepik and NIAID – Human Natural Killer Cell, CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=62609558)