Transcript The influence of psyche on the immune system

The 2nd International Congress of
International Prof. Dr. Alireza Yalda Academic Foundation
in Medical Sciences
24-27 October 2011, Tehran, Iran
The influence of psyche on the immune
system
Prof. Alireza Ranjbar,
MD,PhD
,
President,
Institute of Interventional
Allergology and Immunology,
Cologne / Bonn, Germany
- In recent years one of the most rapidly advancing areas
in medicine has been immunology and its interactions
with various psychological states.
- Considerable data indicate that psychological disorders
may increase an organism's vulnerability to certain
diseases by means of exerting an immunosuppressive
effect, especially those diseases intimately associated
with immunologic mechanisms, such as infection,
malignancy, and autoimmune diseases.
- Significant evidence suggests that the immune system is
capable of profoundly affecting central nervous system
(CNS).
Inflammation and the pathogenesis of depression
Charles L. Raison, et al., Atlanta, USA, 2005
Depression has been linked to a worse outcome in multiple
medical disorders
Increasing amounts of data suggest that inflammatory responses
have an important role in the pathophysiology of depression.
Depressed patients have higher levels of
- proinflammatory cytokines,
- acute phase proteins,
- chemokines and
- cellular adhesion molecules.
Inflammation and the pathogenesis of depression
Charles L. Raison, et al., Atlanta, USA, 2005
Proinflammatory cytokines interact with
- neurotransmitter metabolism,
- neuroendocrine function,
- synaptic plasticity and
- behavior
that characterize depression.
Inflammation and the pathogenesis of depression
Charles L. Raison, et al., Atlanta, USA, 2005
Stress, which can precipitate depression, can also promote
inflammatory responses through effects on sympathetic and
parasympathetic nervous system pathways.
Depression might be a behavioralby product of early adaptive
advantages conferred by genes that promote inflammation.
These findings suggest that targeting proinflammatory cytokines
and their signaling pathways might represent a novel strategy to
treat depression.
Psyche , CNS and Immune System
Experimental and clinical trials
The influence of CNS on Immune System
Experimental studies
In animal trials by directly stimulating the brain,
different investigators have produced alterations
in the immune response.
• Lesions in the dorsal hypothalamus of rabbits
have been shown to suppress both humoral and
cellular immunity.
(Korneva EA, Khai LM, Fiziol Zh SSSR, 49:42-48, 1963)
• Mesencephalic stimulation and electrical
stimulation of the lateral hypothalamus in rats
enhance antibody responses.
(Korneva EA, Khai LM, Fiziol Zh SSSR,53:42-47, 1967 )
• Bilateral anterior hypothalamic lesions in guinea
pigs protect against lethal anaphylaxis
(Freedman DX, Fenichel G, Arch Neurol Psychiatr, 79:164-169, 1958;
Szentivanyi A, Filipp G Ann Allergy 16:143-151, 1958 ; Luparello TJ, Stein M,
Park DC:, Am J Physiol. 207:911-914, 1964 )
The influence of Immune System on CNS
Experimental studies
Corticotropin-releasing factor (CRF) and vasopressin
(VP) mRNA levels in adult rats after Injection with IL-1ß
Indomethacin reduces ACTH response to
iv. IL-1ß
ACTH secretion in rats by IL-1ß Injection with and without
anti-CRF treatment
Time course of the neurochemical
Response to IL-1ß in mice
Human studies
Clinical trials
Human studies
Example 1
Stress and Immune System
-
In a human study, bereavement was found to be
associated with depressed lymphocyte function. In this
study there was a 10-fold difference in T-cell function at 5
weeks between the 26 bereaved spouses and the
controls.
Human studies
Example 2
Depression and Cancer
Depressive Symptoms and Prospective Incidence of
Colorectal Cancer in Women
C. H. Kroenke, G. BennettAmerican Journal of Epidemiology 2005 162(9):839-848
- The authors examined depressive symptoms and prospective
incidence of colorectal cancer and distal colorectal adenomas in
81,612 women without prior cancer from the Nurses' Health
Study
- 400 cases of colorectal cancer and 680 distal colorectal
adenomas accrued between 1992 and the year 2000.
- Depressive symptoms were assessed in 1992 and 1996 with the
five-question Mental Health Index (MHI-5), a subscale of the
Short-Form 36 health status survey.
Depressive Symptoms and Prospective Incidence of
Colorectal Cancer in Women
C. H. Kroenke, G. BennettAmerican Journal of Epidemiology 2005 162(9):839-848
Scores ranged from 0 to 100, and women with scores between 0
and 52 were defined as having significant depressive
symptomatology.
The authors also created four categories across the range of
Mental Health Index scores: 0–52, 53–75, 76–85, and 86–100
(referent).
Depressive Symptoms and Prospective Incidence of
Colorectal Cancer in Women
C. H. Kroenke, G. BennettAmerican Journal of Epidemiology 2005 162(9):839-848
Results:
Women with the highest levels of depressive symptoms had an
elevated risk of incident colorectal cancer (hazard ratio = 1.43,
95% confidence interval: 0.97, 2.11) compared with women with
the lowest levels of symptoms (ptrend = 0.04).
Associations appeared stronger in overweight women. However,
depressive symptoms were unrelated to risk of colorectal
adenomas.
Associations are consistent with a possible role in late promotion
of the disease.
Human studies
Example 3
Stress and Autoimmune Disease
Rheumatoid arthritis and depression
The role of pro-inflammatory cytokine-induced SAPK/MAPK and JAK/STAT
Malemud CJ, Miller AH,Ohio 44106-5076, USA
Expert Opin Ther Targets. 2008 Feb;12(2):171-83
Adult rheumatoid arthritis (RA) patients are frequently clinically
depressed
Peripheral inflammation in RA may influence
- neurotransmitter metabolism,
- neuroendocrine function,
- synaptic plasticity, as well as
- growth factor production,
which can modify neural circuitry and contribute to depression.
Rheumatoid arthritis and depression
The role of pro-inflammatory cytokine-induced SAPK/MAPK and JAK/STAT
Malemud CJ, Miller AH,Ohio 44106-5076, USA
Expert Opin Ther Targets. 2008 Feb;12(2):171-83
A convergence between pro-inflammatory cytokine-induced
synovial joint inflammation in RA and the effects of
pro-inflammatory cytokines on the brain may occur through
activation of the stress-activated/mitogen-activated protein kinases
(SAPK/MAPK) and/or Janus kinase/signal transducers and
activators of transcription (JAK/STAT) pathways.
Rheumatoid arthritis and depression
The role of pro-inflammatory cytokine-induced SAPK/MAPK and JAK/STAT
Malemud CJ, Miller AH, Ohio 44106-5076, USA
Expert Opin Ther Targets. 2008 Feb;12(2):171-83
Some novel anti-depression drugs that were employed in animal
models of 'sickness behavior' and in human depression clinical
trials suppressed clinical markers of inflammation, as well as
SAPK/MAPK and/or JAK/STAT signaling in vitro.
Modifying pro-inflammatory cytokine signaling pathways in the
brain with antidepressants may also be useful in ameliorating
peripheral inflammation in RA
Human studies
Example 4
Depression and Infectious Disease
Depressive symptoms and viral clearance in patients
receiving interferon-α and ribavirin for hepatitis C
Charles L. Raisona, Sherry D. Broadwella, Andrey S. Borisova, et al., USA, 2004
Interferon (IFN)-α plus ribavirin is an effective treatment for
hepatitis C virus (HCV) infection, but is associated with a high rate
of depression.
Therapeutic administration of the cytokine interferon-α leads to
depression in up to 50% of patients.
Depression has been linked to a worse outcome in multiple
medical disorders including viral illnesses.
The authors examined whether increased symptoms of
depression during IFN-α/ribavirin therapy were associated with a
reduced treatment response as assessed by clearance of HCV.
Depressive symptoms and viral clearance in patients
receiving interferon-α and ribavirin for hepatitis C
Charles L. Raisona, Sherry D. Broadwella, Andrey S. Borisova, et al., USA, 2004
Methods:
Depressive symptoms were evaluated in 102 HCV-infected
patients at baseline and after 4, 8, 12, and 24 weeks of pegylated
IFN-α-2b plus ribavirin therapy using the Zung self-rating
depression scale (SDS).
Viral clearance was determined at 24 weeks by polymerase chain
reaction (PCR).
Depressive symptoms and viral clearance in patients
receiving interferon-α and ribavirin for hepatitis C
Charles L. Raisona, Sherry D. Broadwella, Andrey S. Borisova, et al., USA, 2004
Results:
- 34% of subjects (10 out of 29) with a 20-point or greater
increase in SDS Index score were HCV PCR negative at 24
weeks,
- 59% (24 out of 41) of patients with a 10–19 point increase in
SDS Index and
- 69% (22 out of 32) of patients with a less than 10 point increase
(χ2=7.6, df=2, p<0.05).
Depressive symptoms and viral clearance in patients
receiving interferon-α and ribavirin for hepatitis C
Charles L. Raisona, Sherry D. Broadwella, Andrey S. Borisova, et al., USA, 2004
Results:
- In addition, a 20-point or greater increase in SDS Index score
during IFN-α/ribavirin therapy significantly predicted failure to
clear virus when considered alone [crude odds ratio (OR), 3.2;
95% confidence interval (CI), 1.3–8.0; p<0.01] or when
controlling for other factors that affected IFN-α treatment
response (adjusted OR, 3.6; 95% CI, 1.3–9.5; p=0.01).
- These findings suggest that individuals who experience
significant increases in depressive symptoms during IFN-α/
ribavirin therapy may be less likely to clear virus, highlighting
the importance of identifying and treating depressive
symptoms in this patient population.
Human studies
Example 5
Stress and Infectious Disease
Immune system, stress and Herpes infection
Schematic outline of the role of Macrophage / Neutrophils
in elimination of microorganisms ( A. Ranjbar )
Macrophage
LTB4
fMLP
C5a
IL-1
IL-6
TNF-alpha
GM-CSF
IL-8
Neutrophils
Lysozyme
Elastase
Collagenase
Muraminidase
Oxygen free radicals
H2O2
OH O2
-
Myeloperoxidase
Elimination of microorganisms
Phagocytosis-index of granulocytes under and without
stress condition (n=26, 12m, 14 f)
100
50
stress
Phagocytosis-index %, mean
50
without stress
108,64
321,34
Phagocytosis-index of monocytes under and without
stress condition(n=26, 12m, 14 f)
100
50
stress
Phagocytosis-index %, mean
50
without stress
108,64
321,34
Respiratory burst of granulocytes after stimulation with PMA
under and without stress condition(n=26, 12m,14 f)
100
50
with stress
50
Respiratory burst (PMA) %,
mean
without stress
72,8
321,34
0
Respiratory burst of monocytes under and without stress condition
(n=26, 12m, 14 f)
100
50
with stress
50
Respiratory burst (PMA) %,
mean
without stress
72,8
321,34
0
TNF-alpha levels after stimulation with E.coli-derived
LPS plus rhIFN-gamma under and without stress condition
(n=26, 12m, 14 f)
1250
with stress
20
without stress
20
TNF-alpha levels
pg/l,mean
1000
750
500
12
2
p < 0.01
250
52
Summary
There is a bidirectional relationship between the CNS /
psychological states and the immune system.
Mental factors such as stress and depression have been shown
to affect immune system functioning.
Stress and depression are associated with worse outcomes in
immune-related disorders including cancer , autoimmune
disorders and infectious diseases.
Summary
Conversely, immune system activation such as during infectious
diseases, cancer, and autoimmune disorders is associated with
the development of behavioral symptoms similar to those seen in
the context of chronic stress or major depression.
These findings implicate a role for the immune system in the
cause of behavioral disorders in a wide range of medical
illnesses.
Finally, a paradigm is proposed in which abnormal functioning of
either the hypothalamic-pituitary-adrenal (HPA) axis or the
inflammatory response system disrupts feedback regulation of
both neuroendocrine and immune systems contributing to the
development of neuropsychiatric and immunologic disorders.
Positive Psychotherapy –
A novel approach in Social
Psychotherapy with a
Transcultural Perspective
discoverd by
Prof. Dr. Nossrat Peseschkian
by the year 1968
in Wiesbaden, Germany
2000 : 1. Peseschkian-Ranjbar-Begegnung als
Referenten in einem Kongress in Hamburg
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