Neuroimmunomodulation最新文献

{"title":"Thymic Innervation Impairment in Experimental Autoimmune Encephalomyelitis.","authors":"Carolina Francelin, Alexandre Borin, Jessica Funari, Fernando Pradella, Leonilda M B Santos, Wilson Savino, Alessandro S Farias","doi":"10.1159/000535859","DOIUrl":"10.1159/000535859","url":null,"abstract":"<p><strong>Introduction: </strong>The thymus is the primary lymphoid organ responsible for normal T-cell development. Yet, in abnormal metabolic conditions as well as an acute infection, the organ exhibits morphological and cellular alterations. It is well established that the immune system is in a tidy connection and dependent on the central nervous system (CNS), which regulates thymic function by means of innervation and neurotransmitters. Sympathetic innervation leaves the CNS and spreads through thymic tissue, where nerve endings interact directly or indirectly with thymic cells contributing to their maintenance and development.</p><p><strong>Methods: </strong>Herein, we hypothesized that brain damage due to an inflammatory process might elicit alterations upon the thymic-CNS neuroimmune axis, altering not just the sympathetic innervation and neurotransmitter release, but also modifying the thymus microenvironment and T-cell development. We used the well-established multiple sclerosis model of experimental autoimmune encephalomyelitis (EAE), to study putative changes in the thymic neural, lymphoid, and microenvironmental compartments.</p><p><strong>Results: </strong>We showed that along with EAE clinical development, thymus morphology, and cellular compartments are affected, altering the peripheric T-cell population and modifying the retrograde thymic communication toward the CNS.</p><p><strong>Conclusion: </strong>Altogether, our data suggest that the thymic-CNS neuroimmune bidirectional axis is compromised in EAE. This imbalance may contribute to an increased and uncontrolled auto-immune reaction.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138830752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Medically Unexplained Symptoms Are Linked to Chronic Inflammatory Diseases: Is There a Role for Frontal Cerebral Blood Oxygen Content?","authors":"Rainer H Straub, Dario Boschiero","doi":"10.1159/000536204","DOIUrl":"10.1159/000536204","url":null,"abstract":"<p><strong>Introduction: </strong>Patients often go to the physician with medically unexplained symptoms (MUS). MUS can be autonomic nervous system-related \"unspecific\" symptoms, such as palpitations, heart rhythm alterations, temperature dysregulation (hand, feet), anxiety, or depressive manifestations, fatigue, somnolence, nausea, hyperalgesia with varying pains and aches, dizziness, etc. Methods: In this real-world study, we investigated MUS in a cohort of unselected outpatients from general practitioners in Italy. It was our aim to increase the understanding of MUS by using principal component analyses to identify any subcategories of MUS and to check a role of chronic inflammatory diseases. Additionally, we studied cerebral blood oxygen (rCBO2) and associations with MUS and chronic inflammatory disease.</p><p><strong>Results: </strong>Participants included 1,597 subjects (50.6 ± 0.4 years, 65%/35% women/men). According to ICD-10 codes, 137 subjects had chronic inflammatory diseases. MUS were checked by a questionnaire with a numeric rating scale and cerebral blood flow with optical techniques. The analyses of men and women were stratified. Psychological symptom severity was higher in the inflamed compared to the non-inflamed group (fatigue, insomnia in women and men; recent mood changes, daytime sleepiness, anxiety, apathy, cold hands only in women; abnormal appetite and heart rhythm problems only in men). Principal component analysis with MUS provided new subcategories: brain symptoms, gut symptoms, and unspecific symptoms. Brain and gut symptoms were higher in inflamed women and men. Chronic inflammatory diseases and pain were tightly interrelated in men and women (p &lt; 0.0001). In women, not in men, average frontal rCBO2 content was higher in inflamed compared to non-inflamed subjects. In men, not in women, individuals with pain demonstrated a lower average frontal rCBO2 content compared to pain-free men. MUS did not relate to rCBO2 parameters.</p><p><strong>Conclusion: </strong>This study shows close relationships between MUS and chronic inflammatory diseases but not between MUS and rCBO2 parameters.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139466832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quick Guide to Evolutionary Medicine in Neuroimmunomodulation: Why \"Evolved for the Benefit of the Species\" Is Not a Valid Argument.","authors":"Carsten Schradin, Adrian V Jaeggi, Francois Criscuolo","doi":"10.1159/000538294","DOIUrl":"10.1159/000538294","url":null,"abstract":"<p><strong>Background: </strong>Evolutionary medicine builds on evolutionary biology and explains why natural selection has left us vulnerable to disease. Unfortunately, several misunderstandings exist in the medical literature about the levels and mechanisms of evolution. Reasons for these problems start from the lack of teaching evolutionary biology in medical schools. A common mistake is to assume that \"traits must benefit the species, as otherwise the species would have gone extinct in the past\" confusing evolutionary history (phylogeny) with evolutionary function (fitness).</p><p><strong>Summary: </strong>Here we summarise some basic aspects of evolutionary medicine by pointing out: (1) Evolution has no aim. (2) For adaptive evolution to occur, a trait does not have to be beneficial to its carrier throughout its entire life. (3) Not every single individual carrying an adaptive trait needs to have higher than average fitness. (4) Traits do not evolve for the benefit of the species. Using examples from the field of neuroimmunomodulation like sickness behaviour (nervous system), testosterone (hormones), and cytokines (immunity), we show how misconceptions arise from not differentiating between the explanatory categories of phylogeny (evolutionary history) and evolutionary function (fitness).</p><p><strong>Key messages: </strong>Evolution has no aim but is an automatism that does not function for the benefit of the species. In evolution, successful individuals are those that maximise the transmission of their genes, and health and survival are just strategies to have the opportunity to do so. Thus, a trait enabling survival of the individual until reproductive age will spread even if at later age the same trait leads to disease and death. Natural and sexual selection do not select for traits that benefit the health or happiness of the individual, but for traits that increase inclusive fitness even if this increases human suffering. In contrast, our humane aim is to increase individual well-being. Evolutionary medicine can help us achieve this aim against evolutionary constraints.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140110887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Behaviorally Conditioned Immune Responses: \"To Learn New Things, Read Old Books and Papers\".","authors":"Manfred Schedlowski, Martin Hadamitzky","doi":"10.1159/000539073","DOIUrl":"10.1159/000539073","url":null,"abstract":"<p><strong>Background: </strong>More than a century ago, experimental work and clinical observations revealed the functional communication between the brain and the peripheral immune system. This is documented on the one hand by studies first demonstrating the effects of catecholamines on the circulation of leukocytes in experimental animals and humans, and on the other hand via the work of Russian physiologist Ivan Petrovic Pavlov and his coworkers, reporting observations that associative learning can modify peripheral immune functions. This work later fell into oblivion since little was known about the endocrine and immune system's function and even less about the underlying mechanisms of how learning, a central nervous system activity, could affect peripheral immune responses.</p><p><strong>Summary: </strong>In this article, we embark on a fascinating exploration of the historical trajectory of behaviorally conditioned immune responses.</p><p><strong>Key message: </strong>We will pay homage to the visionary scientists who laid the groundwork for this field of research, tracing its evolution from early theories of how associative learning can affect immunity to the modern-day insights that behavioral conditioning of pharmacological responses can be exploited to improve the efficacy of medical interventions for patients.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140860978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum.","authors":"","doi":"10.1159/000540060","DOIUrl":"https://doi.org/10.1159/000540060","url":null,"abstract":"","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sympathetic-Immune Interactions during Different Types of Immune Challenge.","authors":"Adriana Del Rey, Hugo Besedovsky","doi":"10.1159/000535467","DOIUrl":"10.1159/000535467","url":null,"abstract":"<p><strong>Background: </strong>The neuro-endocrine regulation of immune functions is based on a complex network of interactions. As part of this series of articles, we refer here to immune-sympathetic interactions that are triggered by different types of immune challenge.</p><p><strong>Summary: </strong>We mention the initial hypothesis that led to the proposal that the sympathetic nervous system (SNS) is involved in immunoregulation. We next refer mainly to our initial work performed at a time when most immunologists were concentrated in clarifying aspects of the immune system that are essential for its regulation from within. The first approach was to explore whether immune responses to innocuous antigens and superantigens can elicit changes in the activity of the SNS, and their potential relevance for the regulation of the activity of the immune system. The following step was to explore whether comparable immune-SNS interactions are detected in different models of diseases with immune components, such as parasitic and viral infections and autoimmune pathologies.</p><p><strong>Key messages: </strong>We pose some general considerations that may at least partially explain seemly discrepant findings, and remark the importance of interpreting immunoregulatory effects of the SNS together with other neuro-endocrine inputs that simultaneously occur when the activity of the immune system changes. Finally, we provide some arguments to re-consider the use of the expression \"reflex\" in immunology.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138441022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain-Thymus Connections in Chagas Disease.","authors":"Florencia Belén González, Wilson Savino, Ana Rosa Pérez","doi":"10.1159/000538220","DOIUrl":"10.1159/000538220","url":null,"abstract":"<p><strong>Background: </strong>The brain and the immune systems represent the two primary adaptive systems within the body. Both are involved in a dynamic process of communication, vital for the preservation of mammalian homeostasis. This interplay involves two major pathways: the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system.</p><p><strong>Summary: </strong>The establishment of infection can affect immunoneuroendocrine interactions, with functional consequences for immune organs, particularly the thymus. Interestingly, the physiology of this primary organ is not only under the control of the central nervous system (CNS) but also exhibits autocrine/paracrine regulatory circuitries mediated by hormones and neuropeptides that can be altered in situations of infectious stress or chronic inflammation. In particular, Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), impacts upon immunoneuroendocrine circuits disrupting thymus physiology. Here, we discuss the most relevant findings reported in relation to brain-thymic connections during T. cruzi infection, as well as their possible implications for the immunopathology of human Chagas disease.</p><p><strong>Key messages: </strong>During T. cruzi infection, the CNS influences thymus physiology through an intricate network involving hormones, neuropeptides, and pro-inflammatory cytokines. Despite some uncertainties in the mechanisms and the fact that the link between these abnormalities and chronic Chagasic cardiomyopathy is still unknown, it is evident that the precise control exerted by the brain over the thymus is markedly disrupted throughout the course of T. cruzi infection.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dimethyl Fumarate Modulates the Immune Environment and Improves Prognosis in the Acute Phase after Ischemic Stroke.","authors":"Chunrui Bo, Jingkai Li, Junjie Wang, Yaxin Zhang, Tao Wu, Mingyang Wang, Shiyue Hou, Yan Liang, Xiyue Zhang, Shufang Zhao, Huixue Zhang, Jianjian Wang, Lihua Wang, Lianmei Zhong","doi":"10.1159/000539589","DOIUrl":"10.1159/000539589","url":null,"abstract":"<p><strong>Introduction: </strong>Dimethyl fumarate (DMF) has shown potential for protection in various animal models of neurological diseases. However, the impact of DMF on changes in peripheral immune organs and the central nervous system (CNS) immune cell composition after ischemic stroke remains unclear.</p><p><strong>Methods: </strong>Eight-week-old C57BL/6J mice with photothrombosis ischemia and patients with acute ischemic stroke (AIS) were treated with DMF. TTC staining, flow cytometry, and immunofluorescence staining were used to evaluate the infarct volume and changes in immune cells in the periphery and the CNS.</p><p><strong>Results: </strong>DMF reduced the infarct volume on day 1 after PT. DMF reduced the percentages of peripheral immune cells, such as neutrophils, dendritic cells, macrophages, and monocytes, on day 1, followed by NK cells on day 3 and B cells on day 7 after PT. In the CNS, DMF significantly reduced the percentage of monocytes in the brain on day 3 after PT. In addition, DMF increased the number of microglia in the peri-infarct area and reduced the number of neurons in the peri-infarct area in the acute and subacute phases after PT. In AIS patients, B cells decreased in patients receiving alteplase in combination with DMF.</p><p><strong>Conclusion: </strong>DMF can change the immune environment of the periphery and the CNS, reduce infarct volume in the acute phase, promote the recruitment of microglia and preserve neurons in the peri-infarct area after ischemic stroke.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytokines in Cerebrospinal Fluid and Chronic Pain in Humans: Past, Present, and Future.","authors":"Alexander H C Rosenström, Jan-Pieter Konsman, Eva Kosek","doi":"10.1159/000540324","DOIUrl":"10.1159/000540324","url":null,"abstract":"<p><strong>Background: </strong>That neuroimmune interaction occurs in chronic pain conditions has been established for over a century, since the discovery of neurogenic inflammation in the periphery. However, the central aspects of neuroimmune interactions have not been fully appreciated until the late 1900s, when a growing interest in how cytokines in the cerebrospinal fluid (CSF) might be relevant in chronic pain conditions emerged. Since then, the field has evolved, and nowadays neuroinflammation is considered to be involved in the pathophysiology of chronic pain. Whether or not pain conditions can be called \"neuroinflammatory\" is a matter of debate. This review summarizes the results from studies investigating cytokines in the CSF in various pain conditions, and critically discusses neuroimmune aspects of pain conditions using previously proposed hallmarks of neuroinflammation as a framework.</p><p><strong>Summary: </strong>Fifty-two papers were summarized and their results evaluated according to (a) the level of the measured cytokines in patients compared to controls, and (b) the correlation between cytokine level and pain intensity. A subdivision based on pain type was also conducted for each of the 52 studies. A total of 49 proteins have been studied in at least 5 studies, 21 of which were upregulated in a majority of studies. IL-8 was specifically upregulated in a majority of studies of nociceptive pain conditions. Regarding correlation to pain intensity, there is a scarcity of data but 31 proteins were upregulated and correlated with pain in at least one study. Of these, 24 proteins were negatively correlated with pain, and 7 were positively correlated. None of the most studied cytokines, such as TNF, IL-1b, IL-6, IL-8, CCL2/MCP1, BDNF, or bNGF, were consistently correlated to pain.</p><p><strong>Key messages: </strong>There is sufficient evidence to say that chronic pain conditions come with an upregulation of several cytokines. However, the majority of correlations to symptomatology seem to be negative, indicating that the cytokines might play a protective role that has not been broadly considered. Calling chronic pain conditions neuroinflammatory seems wrong; instead, a more suitable term for depicting the findings would, perhaps, be to talk about neuroimmune activation.</p>","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2nd European Psychoneuroimmunology Network (EPN) Autumn School: The skin-brain axis and the breaking of barriers","authors":"","doi":"10.1159/000533642","DOIUrl":"https://doi.org/10.1159/000533642","url":null,"abstract":"","PeriodicalId":19133,"journal":{"name":"Neuroimmunomodulation","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46142806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}