Learned Placebo Effects in the Immune System

2014 ◽  
Vol 222 (3) ◽  
pp. 148-153 ◽  
Author(s):  
Sabine Vits ◽  
Manfred Schedlowski

Associative learning processes are one of the major neuropsychological mechanisms steering the placebo response in different physiological systems and end organ functions. Learned placebo effects on immune functions are based on the bidirectional communication between the central nervous system (CNS) and the peripheral immune system. Based on this “hardware,” experimental evidence in animals and humans showed that humoral and cellular immune functions can be affected by behavioral conditioning processes. We will first highlight and summarize data documenting the variety of experimental approaches conditioning protocols employed, affecting different immunological functions by associative learning. Taking a well-established paradigm employing a conditioned taste aversion model in rats with the immunosuppressive drug cyclosporine A (CsA) as an unconditioned stimulus (US) as an example, we will then summarize the efferent and afferent communication pathways as well as central processes activated during a learned immunosuppression. In addition, the potential clinical relevance of learned placebo effects on the outcome of immune-related diseases has been demonstrated in a number of different clinical conditions in rodents. More importantly, the learned immunosuppression is not restricted to experimental animals but can be also induced in humans. These data so far show that (i) behavioral conditioned immunosuppression is not limited to a single event but can be reproduced over time, (ii) immunosuppression cannot be induced by mere expectation, (iii) psychological and biological variables can be identified as predictors for this learned immunosuppression. Together with experimental approaches employing a placebo-controlled dose reduction these data provide a basis for new therapeutic approaches to the treatment of diseases where a suppression of immune functions is required via modulation of nervous system-immune system communication by learned placebo effects.

2017 ◽  
Vol 6 (2) ◽  
pp. 146
Author(s):  
Abdelaziz Ghanemi ◽  
Besma Boubertakh

<span lang="EN-US">The immune system plays key roles in the defense of the organism. However, the effects of the immune system are not limited to the immune functions and have impacts beyond the anti-pathogenes role.                          Indeed, neuroimmunology is a representative field of how the immune system affects non-immune biological and physio-pathological functions. Herein, we have selected a number of neurodegenerative diseases as illustrative examples to put a spotlight on this important field.              Importantly, clarifying the links and interactions between the immune system and the nervous system represents key elements for the understanding neurodegenerative diseases since it will lead to new theories about the pathogenesis and the mechanisms underlying the related processes and thus, provide us with new data and novel tools to both describe the related pathways and develop new therapeutic approaches as well as diagnostic approaches and research methodologies based on such new discoveries.</span>


2011 ◽  
Vol 366 (1572) ◽  
pp. 1799-1807 ◽  
Author(s):  
Sabine Vits ◽  
Elvir Cesko ◽  
Paul Enck ◽  
Uwe Hillen ◽  
Dirk Schadendorf ◽  
...  

Current placebo research postulates that conditioning processes are one of the major mechanisms of the placebo response. Behaviourally conditioned changes in peripheral immune functions have been demonstrated in experimental animals, healthy subjects and patients. The physiological mechanisms responsible for this ‘learned immune response’ are not yet fully understood, but some relevant afferent and efferent pathways in the communication between the brain and the peripheral immune system have been identified. In addition, possible benefits and applicability in clinical settings have been demonstrated where behaviourally conditioned immunosuppression attenuated the exacerbation of autoimmune diseases, prolonged allograft survival and affected allergic responses. Here, we summarize data describing the mechanisms and the potential clinical benefit of behaviourally conditioned immune functions, with particular focus on learned placebo effects on allergic reactions.


2017 ◽  
Vol 6 (2) ◽  
pp. 146
Author(s):  
Abdelaziz Ghanemi ◽  
Besma Boubertakh

The immune system plays key roles in the defense of the organism. However, the effects of the immune system are not limited to the immune functions and have impacts beyond the anti-pathogenes role. Indeed, neuroimmunology is a representative field of how the immune system affects non-immune biological and physio-pathological functions. Herein, we have selected a number of neurodegenerative diseases as illustrative examples to put a spotlight on this important field. Importantly, clarifying the links and interactions between the immune system and the nervous system represents key elements for the understanding neurodegenerative diseases since it will lead to new theories about the pathogenesis and the mechanisms underlying the related processes and thus, provide us with new data and novel tools to both describe the related pathways and develop new therapeutic approaches as well as diagnostic approaches and research methodologies based on such new discoveries.


2019 ◽  
Vol 4 (4) ◽  
pp. 01-05
Author(s):  
Trevor Archer

Interactions between neurodegenerative states and immune system dysregulations may underlie several diseases that induce problems for neuropsychological and physical health. It seems increasingly evident that process of apoptosis, a central issue for health and well-being, is associated to greater or lesser extents with the balance and ongoing regulation of immune system proclivities. One key contributor to the regulation of structure and function of brain and behaviour has emerged to be the gastrointestinal microbiome, not least in the context of the neurodegenerative disorders. Certain genes identified in in these disorders encode for proteins with directly-acting immunoactive/immunoreactive roles, which when mutated lead to dysregulations in immune functions, thereby affecting the disease states; yet accumulating evidence implies direct malfunctions of immune ells in the brain and CNS as well as at the periphery of the nervous system. Remarkably, the therapeutic effects of anti-tumor, immune system-enhancing agents are emerging to awaken the necessity for consideration of immune system-nervous system interactions as reciprocal determinants of both neurodegenerative and inflammatory disorders.


2020 ◽  
Vol 21 (3) ◽  
pp. 288-301 ◽  
Author(s):  
Lin Zhou ◽  
Luyao Ao ◽  
Yunyi Yan ◽  
Wanting Li ◽  
Anqi Ye ◽  
...  

Background: Some of the current challenges and complications of cancer therapy are chemotherapy- induced peripheral neuropathy (CIPN) and the neuropathic pain that are associated with this condition. Many major chemotherapeutic agents can cause neurotoxicity, significantly modulate the immune system and are always accompanied by various adverse effects. Recent evidence suggests that cross-talk occurs between the nervous system and the immune system during treatment with chemotherapeutic agents; thus, an emerging concept is that neuroinflammation is one of the major mechanisms underlying CIPN, as demonstrated by the upregulation of chemokines. Chemokines were originally identified as regulators of peripheral immune cell trafficking, and chemokines are also expressed on neurons and glial cells in the central nervous system. Objective: In this review, we collected evidence demonstrating that chemokines are potential mediators and contributors to pain signalling in CIPN. The expression of chemokines and their receptors, such as CX3CL1/CX3CR1, CCL2/CCR2, CXCL1/CXCR2, CXCL12/CXCR4 and CCL3/CCR5, is altered in the pathological conditions of CIPN, and chemokine receptor antagonists attenuate neuropathic pain behaviour. Conclusion: By understanding the mechanisms of chemokine-mediated communication, we may reveal chemokine targets that can be used as novel therapeutic strategies for the treatment of CIPN.


2020 ◽  
Vol 20 (4) ◽  
pp. 546-557
Author(s):  
Anna Rizzi ◽  
Matteo Saccia ◽  
Vincenzo Benagiano

Background: According to the views of psychoneuroendocrinoimmunology, many interactions exist between nervous, endocrine and immune system the purpose of which is to achieve adaptive measures restoring an internal equilibrium (homeostasis) following stress conditions. The center where these interactions converge is the hypothalamus. This is a center of the autonomic nervous system that controls the visceral systems, including the immune system, through both the nervous and neuroendocrine mechanisms. The nervous mechanisms are based on nervous circuits that bidirectionally connect hypothalamic neurons and neurons of the sympathetic and parasympathetic system; the neuroendocrine mechanisms are based on the release by neurosecretory hypothalamic neurons of hormones that target the endocrine cells and on the feedback effects of the hormones secreted by these endocrine cells on the same hypothalamic neurons. Moreover, the hypothalamus is an important subcortical center of the limbic system that controls through nervous and neuroendocrine mechanisms the areas of the cerebral cortex where the psychic functions controlling mood, emotions, anxiety and instinctive behaviors take place. Accordingly, various studies conducted in the last decades have indicated that hypothalamic diseases may be associated with immune and/or psychic disorders. Objective: Various researches have reported that the hypothalamus is controlled by the cerebellum through a feedback nervous circuit, namely the hypothalamocerebellar circuit, which bi-directionally connects regions of the hypothalamus, including the immunoregulatory ones, and related regions of the cerebellum. An objective of the present review was to analyze the anatomical bases of the nervous and neuroendocrine mechanisms for the control of the immune system and, in particular, of the interaction between hypothalamus and cerebellum to achieve the immunoregulatory function. Conclusion: Since the hypothalamus represents the link through which the immune functions may influence the psychic functions and vice versa, the cerebellum, controlling several regions of the hypothalamus, could be considered as a primary player in the regulation of the multiple functional interactions postulated by psychoneuroendocrinoimmunology.


Author(s):  
Katarzyna Curzytek ◽  
Monika Leśkiewicz

AbstractSince affective disorders are considered to be underlain by the immune system malfunction, an important role in their pathophysiology is assigned to the proinflammatory mediators. Recently, chemokines, the group of chemotactic cytokines, have become a focus for basic and clinical scientists in the context of the development and treatment of brain diseases. Among them, chemokine CCL2 and its main receptor CCR2 have become candidate mediators of abnormal brain-immune system dialogue in depression. Besides the chemotactic activity, the CCL2-CCR2 axis is involved in various neurobiological processes, neurogenesis, neurotransmission, neuroinflammation, neurodegeneration, as well as neuroregeneration. Given the range of immunomodulatory possibilities that the CCL2-CCR2 pair can exert on the nervous system, its proinflammatory properties were initially thought to be a major contributor to the development of depressive disorders. However, further research suggests that the malfunctions of the nervous system are rather associated with impaired homeostatic properties manifested by the CCL2-CCR2 dyad dysfunctions. This review aims to present literature data on the action of the CCL2-CCR2 axis in the central nervous system under physiological and pathological conditions, as well as the contribution of this ligand-receptor system to the processes underlying affective disorders. Additionally, this article draws attention to the importance of the CCL2-CRR2 pathway as a potential pharmacological target with antidepressant potential.


Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 699
Author(s):  
Cielo García-Montero ◽  
Oscar Fraile-Martínez ◽  
Ana M. Gómez-Lahoz ◽  
Leonel Pekarek ◽  
Alejandro J. Castellanos ◽  
...  

The most prevalent diseases of our time, non-communicable diseases (NCDs) (including obesity, type 2 diabetes, cardiovascular diseases and some types of cancer) are rising worldwide. All of them share the condition of an “inflammatory disorder”, with impaired immune functions frequently caused or accompanied by alterations in gut microbiota. These multifactorial maladies also have in common malnutrition related to physiopathology. In this context, diet is the greatest modulator of immune system–microbiota crosstalk, and much interest, and new challenges, are arising in the area of precision nutrition as a way towards treatment and prevention. It is a fact that the westernized diet (WD) is partly responsible for the increased prevalence of NCDs, negatively affecting both gut microbiota and the immune system. Conversely, other nutritional approaches, such as Mediterranean diet (MD), positively influence immune system and gut microbiota, and is proposed not only as a potential tool in the clinical management of different disease conditions, but also for prevention and health promotion globally. Thus, the purpose of this review is to determine the regulatory role of nutritional components of WD and MD in the gut microbiota and immune system interplay, in order to understand, and create awareness of, the influence of diet over both key components.


2021 ◽  
Author(s):  
Qiushuang Zhang ◽  
Yuanyuan Guo ◽  
Lijuan Zhu ◽  
Xinlong Liu ◽  
Jiapei Yang ◽  
...  

Immune system plays a key role in restraining the tumor progression. Therefore, enhancing immune functions using immune stimulants, such as unmethylated CpG oligonucleotides, have emerged as a promising strategy for...


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