Two recent studies indicate that job stress, anxiety and insomnia may affect natural killer (NK) cell activity.
Background:
Natural killer (NK) cells, key players in innate immunity, swiftly identify and eliminate virus-infected or abnormal cells without prior sensitization. By lysing transformed or infected cells, they limit tumor growth and viral infections. Thus, reduced NKA has been associated with an increased susceptibility to infections and increased risk of various types of cancer.
It appears that NK cells are the most ‘sensitive’ cells to the suppressive effect of stress, and not surprisingly, in the past, NK cell activity has been used as a bona fide index of stress-induced suppression of cellular immunity (for review see M. Irwin, 1994). The potent suppressive effect of CAs on NK cell activity is probably due to the fact that NK cells possess the highest number of β2-ARs among lymphoid cells.
Burnout is a psychological response resulting from a chronic stress reaction and is frequently observed in healthcare workers. As per the American Nurses Association a 2020 survey indicated that almost two-thirds of nurses (62%) experience burnout. It’s especially common among younger nurses, with 69% of nurses under 25 reporting burnout.
Generalized anxiety disorder (GAD), a common mental condition is frequently associated with sleep disturbances. The prevalence of GAD has increased dramatically over the last few decades, with women being more likely to be affected than men. Recent studies have shown that anxiety-related disorders increase the risk of development of cardiovascular disease morbidity, such as coronary heart disease, heart failure, and stroke (cf. Alhamawi et al., 2025).
We reported that GAD affects levels of cytokines such as IFN-γ, TNF-α and IL-10, and discussed the role of anxiety in asthma and dementia; and the involvement of Substance P and low levels of oxytocin with anxiety in children.
The two recent studies discussed here:
A 2005 study by Yuko Morikawa et al. investigated the effects of job stress on NK cell activity and the proportion and cell numbers of the NK cell subset: CD16+56+lymphocytes in 61 female nurses aged 23–59, who worked in a public psychiatric hospital in Ishikawa, Japan.
The authors used the Nursing Job Stressor scale as a measure of chronic professional stress. This Nursing Job Stressor scale included seven subscales or groups of job stress.
The investigators found that quantitative work load was inversely related to NK cell activity with statistical significance, and the proportion and cell counts of CD16+56+ lymphocyte also tended to decrease with quantitative work load. The authors considered that the decrement of NK cell activity with quantitative work load was due to a decrease in the number of NK cells.
Thus, this study revealed that quantitative work load was the strongest predictor for NK cell function among seven subscales of job stress for nurses. Interestingly, quantitative work load was found to predict the syndrome of burnout as measured by the Maslach Burnout Inventory (MBI), and was considered to be a primary factor for the burnout syndrome in a cross sectional study among Japanese nurses.
The authors of this study concluded that the perceived job stress, particularly quantitative work load, is able to reduce NK cell activity through a decrease in NK cell numbers. They discussed that psychological mechanisms in stress may contribute to altered or reduced cellular immune function. And, whether these immunological changes are associated with vulnerability or not, remains to be clarified.
A 2025 cross-sectional study by Alhamawi et al. was conducted in female students under 25 years of age; 60 participants were recruited for this study at the Taibah University in Madinah, Saudi Arabia.
The authors found that in this study approximately 75% of female students reported GAD at different levels of severity, and 50% reported sleeping disturbance suggestive of insomnia.
The investigators reported a significant reduction of NK cells, observed in participants experiencing severe GAD-7 symptoms. The negative association between the frequency and number of circulating NK cells and the total scores of GAD-7 was observed among students who reported experiencing insomnia.
Of note, these investigators found that students with symptoms of GAD-7 had a lower percentage and number of circulatory NK cells and their subpopulation—CD16+CD56dim and CD16+CD56high—compared to normal students.
The authors discussed that there is an urgent need to investigate how anxiety and sleep disturbance impact immune function. According to these authors, understanding how these psychological stressors influence the distribution and activity of immune cells, especially peripheral NK cells, may provide valuable insights into the mechanisms underlying inflammation and tumorigenesis.
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