The influence of Psychological Intervention upon Neuro-Endocrine-Immune Interaction

Akira Naito1, 2, Tannis M. Laidlaw1, John H. Gruzelier1,Don C. Henderson2

1. Division of Neuroscience and Mental Health

2. Department of Immunology

Faculty of Medicine, Imperial College London

 

Background: Stress affects both mental and physical well-being. A growing body of evidence suggests that there are cross regulatory influences between psychological, nervous, endocrine and immune systems. This has led to the proposal of a psycho-neuro-endocrine-immune network, in which a change in one aspect has consequential influences upon other parts of the network. This project is based on the hypothesis that psychological intervention may counteract the detrimental effects of stress both on psychological well-being and on general health.

Investigative approach: The psychological intervention utilised a Japanese stress management system, called Johrei, and self-hypnosis to investigate phenomenological associations between stress perception, stress hormone levels, and immune profile in university students facing exams. These associations are also examined in vitro to determine any direct links between stress hormone levels and the immune parameters.

Results: The students who had increased stress levels, defined by the perceived stress scale, exhibited decreased levels of natural killer (NK) cells and the NK cytotoxic activity (NKCA), and increased CD4 T-cell levels. Individuals practising self-hypnosis did not show these stress associated changes. Further, those practising Johrei had an increase in NK cell levels and a decrease in the CD4 T-cell levels.  In vitro cortisol, a major stress hormone inhibited T-cell proliferation in a dose-dependent manner and decreased the levels of NKCA in human peripheral blood mononuclear cells. The decrease in the levels of NKCA was not associated with a change in cell numbers and distribution between regulatory and cytotoxic NK cells, but was related to the expression of major lysis receptors on NK cells.

Conclusions: These findings support the hypothesis that psychological intervention may counteract the detrimental effects of stress both on psychological well-being and on general health mediated through the psycho-neuro-endocrine-immune network.  More research is needed to explore the mechanisms of this network.

 

Presented at the Annual Meeting for Clinician Scientist in Training

London on 28 February 2005

 

The influence of psychological interventions upon stress related changes

1. In exam associated stress in university students

 

Akira Naito1, 2, Tannis Laidlaw1, Prabuddh Dwivedi1, John Gruzelier1, Don Henderson2

1. Division of Neuroscience and Mental Health

2. Department of Immunology

Faculty of Medicine, Imperial College London

 

Hypothesis: This series of investigation is based upon the hypothesis that psychological intervention may counteract the detrimental effects of stress both on psychological well-being and on general health.

Background: Stress affects both mental and physical well-being. A growing body of evidence suggests that there are cross regulatory influences between psyche, nervous, endocrine and immune systems. This has led to the proposal of an interactive psycho-neuro-endocrine-immune (P-N-E-I) network, in which a change in one aspect has consequential influences upon other parts of the network.

Investigative approach: There are four components to these investigations - two in vivo studies and two in vitro investigations. The current in vivo study investigates stress and the effects of psychological interventions in university students facing exams. The psychological interventions were self-hypnosis and a Japanese stress management system, called Johrei. The associations between stress perception, stress hormone levels, and immune profiles were examined.

Results: The students who had increased stress levels, defined by the perceived stress scale, exhibited decreased levels of natural killer (NK) cells and the NK cytotoxic activity (NKCA), and increased CD4 T-cell levels. Individuals practising self-hypnosis did not show these stress associated changes. Further, those practising Johrei had an increase in NK cell levels and a decrease in the CD4 T-cell levels.

Conclusions: Results support the hypothesis that psychological intervention may counteract the effects of stress both on psychological well-being and on general health mediated through the interactive P-N-E-I network.  More research is warranted to explore the mechanisms of this network.

 

To be presented at the 18th World Congress on Psychosomatic Medicine

Kobe on 22-26 August 2005

 

The influence of psychological interventions upon stress related changes

2. In disease associated stress in HIV-infected patients

 

Akira Naito1, 2, Tannis Laidlaw1, Bryan, Bennett1, John Gruzelier1, Simon Burton3, Don Henderson2

1. Division of Neuroscience and Mental Health

2. Department of Immunology

3. HIV/GUM Directorate

Faculty of Medicine, Imperial College London

 

Hypothesis: This series of investigation is based upon the hypothesis that psychological intervention may counteract the detrimental effects of stress both on psychological well-being and on general health.

Background: HIV infection may be considered to be a life-long biological and psychological stressor leading to detrimental outcomes associated with disease progression. Stress reduction in these patients may have beneficial effects through delaying disease progression via the proposed interactive psycho-neuro-endocrine-immune (P-N-E-I) network.

Investigative approach: Self-hypnosis and a Japanese non-touching, laying-on-of hands-like technique, called Johrei, were used to investigate the effects of psychological intervention upon immune parameters (especially in CD4 counts) associated with disease progression along with phenomenological associations between stress perception and stress hormone levels in HIV-infected patients on no medication.

Results: The CD4 T-cell counts of HIV-infected patients showed a steady decline of 5-10 cells/mL/month. The declining gradient of the CD4 T-cell counts was reduced after psychological interventions. The NK cell counts and the viral load levels did not show any consistent trends. Stress perception and hormone levels are currently being analysed.

Conclusions: Psychological intervention, particularly Johrei, alleviated the rate of steadily decline in CD4 T-cell counts. This in part supports the hypotheses that psychological intervention may be beneficial through maintaining CD4 T-cell counts in HIV-infected patients. Further research employing larger numbers of subjects is needed to explore the mechanisms of the interactive P-N-E-I network.

 

To be presented at the 18th World Congress on Psychosomatic Medicine

Kobe on 22-26 August 2005

 

Stress related changes associated with in vitro exposure to cortisol

1. Effects upon Natural Killer cells

 

Akira Naito, Ijeoma C. Ugwu-Onuoha, Don C. Henderson

Department of Immunology

Faculty of Medicine, Imperial College London

 

 

Hypothesis: This series of investigation is based upon the hypothesis that psychological intervention may counteract the detrimental effects of stress on both psychological well-being and general health, mediated via an interactive psycho-neuro-endocrine-immune (P-N-E-I) network.

Background: Psychological stress may suppress or enhance immune functions, depending upon the nature and duration of the stress and the immune parameters under consideration. Natural Killer (NK) cells are essential components of the innate immune system providing the first line of defence against infection and malignancy. Increased and un-fluctuated cortisol levels are a common feature of stress responses.

Investigative approach: In this investigation in vitro cortisol exposure over 24 hours has been used to examine the effects of stress upon human NK cells.

Results: NK cytotoxic activity (NKCA) was increased after 24hrs in vitro incubation of human peripheral blood mononuclear cells (PBMCs).  Exposure of PBMCs to cortisol induced a dose-dependent inhibition in the increased NKCA. This inhibition was not associated with an alteration in NK (CD3-CD56+) cell numbers, nor in the distribution between cytotoxic (CD56dimCD16+) and regulatory (CD56brightCD16-) NK cells. The inhibition, however, was related to the expression of Natural Cytotoxic Receptors (NCRs: NKp30 and NKp46), which are major natural lysis receptors on NK cells.

Conclusions: The stress hormone, cortisol, has inhibitory effects upon the levels of the NKCA, which appears to be moderated through natural lysis receptors on the cytotoxic NK cells. This in part supports the hypothesis that stress can detrimentally influence the immune system via the interactive P-N-E-I network.

 

To be presented at the 18th World Congress on Psychosomatic Medicine

Kobe on 22-26 August 2005

 

Stress related changes associated with in vitro exposure to cortisol

2. Effects upon T-lymphocytes

 

Akira Naito, Don C. Henderson

Department of Immunology

Faculty of Medicine, Imperial College London

 

Hypothesis: This series of investigation is based upon the hypothesis that psychological intervention may counteract the detrimental effects of stress on both psychological well-being and general health, mediated via a cross regulatory psycho-neuro-endocrine-immune (P-N-E-I) network.

Background: T-lymphocytes play a major role in responding against infection and malignancy. In the endocrine system, chronic psychological stress leads to increased cortisol levels reflected by an alteration in the circadian pattern with increased baseline levels but reduced peak values.

Investigative approach: In vitro exposure to cortisol has been used to simulate the effects of chronic stress on human peripheral blood mononuclear cells in the current investigation. Proliferative responses to phytohaemagglutinin (PHA), Streptococcus Enterotoxin B (SEB), mycobacterial proteins and herpes antigen, and expression of surface activation and apoptosis markers on T-lymphocytes were used to examine the effect of cortisol.

Results: The results showed that cortisol inhibits in vitro lymphocyte proliferative responses following stimulation with memory recall antigens, mitogen (PHA) and super antigen (SEB). Inhibition of the PHA dependent proliferation was not associated with an alteration in distribution of lymphocyte sub-populations or with the expressions of surface markers for activation (CD25) and apoptosis (CD95 and Annexin-V).

Conclusions: The stress hormone, cortisol, has inhibitory actions upon T-lymphocyte proliferative responses. This further supports the concept that stress can detrimentally influence the immune system via the interactive P-N-E-I network.

 

To be presented at the 18th World Congress on Psychosomatic Medicine

Kobe on 22-26 August 2005