Stroke-induced immunodeficiency promotes spontaneous bacterial infections and is mediated by sympathetic activation reversal by poststroke T helper cell type 1-like immunostimulation.
01 Sep 2003-Journal of Experimental Medicine (The Rockefeller University Press)-Vol. 198, Iss: 5, pp 725-736
TL;DR: It is suggested that a catecholamine-mediated defect in early lymphocyte activation is the key factor in the impaired antibacterial immune response after stroke.
Abstract: Infections are a leading cause of death in stroke patients. In a mouse model of focal cerebral ischemia, we tested the hypothesis that a stroke-induced immunodeficiency increases the susceptibility to bacterial infections. 3 d after ischemia, all animals developed spontaneous septicemia and pneumonia. Stroke induced an extensive apoptotic loss of lymphocytes and a shift from T helper cell (Th)1 to Th2 cytokine production. Adoptive transfer of T and natural killer cells from wild-type mice, but not from interferon (IFN)-γ–deficient mice, or administration of IFN-γ at day 1 after stroke greatly decreased the bacterial burden. Importantly, the defective IFN-γ response and the occurrence of bacterial infections were prevented by blocking the sympathetic nervous system but not the hypothalamo-pituitary-adrenal axis. Furthermore, administration of the β-adrenoreceptor blocker propranolol drastically reduced mortality after stroke. These data suggest that a catecholamine-mediated defect in early lymphocyte activation is the key factor in the impaired antibacterial immune response after stroke.
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TL;DR: The article covers referral and emergency management, Stroke Unit service, diagnostics, primary and secondary prevention, general stroke treatment, specific treatment including acute management, management of complications, and rehabilitation.
Abstract: This article represents the update of the European Stroke Initiative Recommendations for Stroke Management. These guidelines cover both ischaemic stroke and transient ischaemic attacks, which are now considered to be a single entity. The article covers referral and emergency management, Stroke Unit service, diagnostics, primary and secondary prevention, general stroke treatment, specific treatment including acute management, management of complications, and rehabilitation.
2,125 citations
Cites background from "Stroke-induced immunodeficiency pro..."
...A brain-mediated immunodepressive state contributes to post-stroke infection [450, 451]....
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TL;DR: Gaining a better understanding of the reciprocal interaction between the immune system and the ischemic brain is essential to harness the full therapeutic potential of the immunology of stroke.
Abstract: Immunity and inflammation are key elements of the pathobiology of stroke, a devastating illness second only to cardiac ischemia as a cause of death worldwide. The immune system participates in the brain damage produced by ischemia, and the damaged brain, in turn, exerts an immunosuppressive effect that promotes fatal infections that threaten the survival of people after stroke. Inflammatory signaling is involved in all stages of the ischemic cascade, from the early damaging events triggered by arterial occlusion to the late regenerative processes underlying post-ischemic tissue repair. Recent developments have revealed that stroke engages both innate and adaptive immunity. But adaptive immunity triggered by newly exposed brain antigens does not have an impact on the acute phase of the damage. Nevertheless, modulation of adaptive immunity exerts a remarkable protective effect on the ischemic brain and offers the prospect of new stroke therapies. As immunomodulation is not devoid of deleterious side effects, a better understanding of the reciprocal interaction between the immune system and the ischemic brain is essential to harness the full therapeutic potential of the immunology of stroke.
1,949 citations
Cites background from "Stroke-induced immunodeficiency pro..."
..., and steroid antagonists and the b-adrenergic receptor antagonist propanolol counteract lymphocyte apoptosis and infection propensity after stroke in rodent model...
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TL;DR: An overview of the time‐dependent recruitment of different inflammatory cells following focal cerebral I/R is provided and certain recent findings and currently unanswered questions about inflammatory cells in the pathophysiology of ischemic stroke are highlighted.
Abstract: Inflammation plays an important role in the pathogenesis of ischemic stroke and other forms of ischemic brain injury. Experimentally and clinically, the brain responds to ischemic injury with an acute and prolonged inflammatory process, characterized by rapid activation of resident cells (mainly microglia), production of proinflammatory mediators, and infiltration of various types of inflammatory cells (including neutrophils, different subtypes of T cells, monocyte/macrophages, and other cells) into the ischemic brain tissue. These cellular events collaboratively contribute to ischemic brain injury. Despite intense investigation, there are still numerous controversies concerning the time course of the recruitment of inflammatory cells in the brain and their pathogenic roles in ischemic brain injury. In this review, we provide an overview of the time-dependent recruitment of different inflammatory cells following focal cerebral I/R. We discuss how these cells contribute to ischemic brain injury and highlight certain recent findings and currently unanswered questions about inflammatory cells in the pathophysiology of ischemic stroke.
1,315 citations
Cites background from "Stroke-induced immunodeficiency pro..."
...phase of stroke [90], which results mainly from immunode-...
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TL;DR: Treg cells are major cerebroprotective modulators of postischemic inflammatory brain damage targeting multiple inflammatory pathways, and IL-10 signaling is essential for their immunomodulatory effect.
Abstract: Systemic and local inflammatory processes have a key, mainly detrimental role in the pathophysiology of ischemic stroke. Currently, little is known about endogenous counterregulatory immune mechanisms. We examined the role of the key immunomodulators CD4(+)CD25(+) forkhead box P3 (Foxp3)(+) regulatory T lymphocytes (T(reg) cells), after experimental brain ischemia. Depletion of T(reg) cells profoundly increased delayed brain damage and deteriorated functional outcome. Absence of T(reg) cells augmented postischemic activation of resident and invading inflammatory cells including microglia and T cells, the main sources of deleterious cerebral tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), respectively. Early antagonization of TNF-alpha and delayed neutralization of IFN-gamma prevented infarct growth in T(reg) cell-depleted mice. Intracerebral interleukin-10 (IL-10) substitution abrogated the cytokine overexpression after T(reg) cell depletion and prevented secondary infarct growth, whereas transfer of IL-10-deficient T(reg) cells in an adoptive transfer model was ineffective. In conclusion, T(reg) cells are major cerebroprotective modulators of postischemic inflammatory brain damage targeting multiple inflammatory pathways. IL-10 signaling is essential for their immunomodulatory effect.
888 citations
TL;DR: Understanding CIDS will allow us to work on developing effective therapeutic strategies, with which the outcome after CNS damage by a host of diseases could be improved by eliminating a major determinant of poor recovery.
Abstract: Infections are a leading cause of morbidity and mortality in patients with acute CNS injury. It has recently become clear that CNS injury significantly increases susceptibility to infection by brain-specific mechanisms: CNS injury induces a disturbance of the normally well balanced interplay between the immune system and the CNS. As a result, CNS injury leads to secondary immunodeficiency - CNS injury-induced immunodepression (CIDS) - and infection. CIDS might serve as a model for the study of the mechanisms and mediators of brain control over immunity. More importantly, understanding CIDS will allow us to work on developing effective therapeutic strategies, with which the outcome after CNS damage by a host of diseases could be improved by eliminating a major determinant of poor recovery.
774 citations
References
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Book•
01 Jan 1994
TL;DR: Cellular and molecular immunology , Cellular and molecular Immunology , کتابخانه الکرونیک و دیجیتال - آذرسا
Abstract: Cellular and molecular immunology , Cellular and molecular immunology , کتابخانه الکترونیک و دیجیتال - آذرسا
3,968 citations
TL;DR: The discovery that cholinergic neurons inhibit acute inflammation has qualitatively expanded understanding of how the nervous system modulates immune responses, and the opportunity now exists to apply this insight to the treatment of inflammation through selective and reversible 'hard-wired' neural systems.
Abstract: Inflammation is a local, protective response to microbial invasion or injury. It must be fine-tuned and regulated precisely, because deficiencies or excesses of the inflammatory response cause morbidity and shorten lifespan. The discovery that cholinergic neurons inhibit acute inflammation has qualitatively expanded our understanding of how the nervous system modulates immune responses. The nervous system reflexively regulates the inflammatory response in real time, just as it controls heart rate and other vital functions. The opportunity now exists to apply this insight to the treatment of inflammation through selective and reversible 'hard-wired' neural systems.
3,146 citations
"Stroke-induced immunodeficiency pro..." refers background in this paper
...Activation of the vagus nerve by inflammatory cytokines during endotoxemia was found to inhibit macrophage cytokine production through release of acetylcholine (24, 25)....
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Journal Article•
TL;DR: The activation of SNS during an immune response might be aimed to localize the inflammatory response, through induction of neutrophil accumulation and stimulation of more specific humoral immune responses, although systemically it may suppress Th1 responses, and, thus protect the organism from the detrimental effects of proinflammatory cytokines and other products of activated macrophages.
Abstract: The brain and the immune system are the two major adaptive systems of the body During an immune response the brain and the immune system "talk to each other" and this process is essential for maintaining homeostasis Two major pathway systems are involved in this cross-talk: the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS) This overview focuses on the role of SNS in neuroimmune interactions, an area that has received much less attention than the role of HPA axis Evidence accumulated over the last 20 years suggests that norepinephrine (NE) fulfills the criteria for neurotransmitter/neuromodulator in lymphoid organs Thus, primary and secondary lymphoid organs receive extensive sympathetic/noradrenergic innervation Under stimulation, NE is released from the sympathetic nerve terminals in these organs, and the target immune cells express adrenoreceptors Through stimulation of these receptors, locally released NE, or circulating catecholamines such as epinephrine, affect lymphocyte traffic, circulation, and proliferation, and modulate cytokine production and the functional activity of different lymphoid cells Although there exists substantial sympathetic innervation in the bone marrow, and particularly in the thymus and mucosal tissues, our knowledge about the effect of the sympathetic neural input on hematopoiesis, thymocyte development, and mucosal immunity is extremely modest In addition, recent evidence is discussed that NE and epinephrine, through stimulation of the beta(2)-adrenoreceptor-cAMP-protein kinase A pathway, inhibit the production of type 1/proinflammatory cytokines, such as interleukin (IL-12), tumor necrosis factor-alpha, and interferon-gamma by antigen-presenting cells and T helper (Th) 1 cells, whereas they stimulate the production of type 2/anti-inflammatory cytokines such as IL-10 and transforming growth factor-beta Through this mechanism, systemically, endogenous catecholamines may cause a selective suppression of Th1 responses and cellular immunity, and a Th2 shift toward dominance of humoral immunity On the other hand, in certain local responses, and under certain conditions, catecholamines may actually boost regional immune responses, through induction of IL-1, tumor necrosis factor-alpha, and primarily IL-8 production Thus, the activation of SNS during an immune response might be aimed to localize the inflammatory response, through induction of neutrophil accumulation and stimulation of more specific humoral immune responses, although systemically it may suppress Th1 responses, and, thus protect the organism from the detrimental effects of proinflammatory cytokines and other products of activated macrophages The above-mentioned immunomodulatory effects of catecholamines and the role of SNS are also discussed in the context of their clinical implication in certain infections, major injury and sepsis, autoimmunity, chronic pain and fatigue syndromes, and tumor growth Finally, the pharmacological manipulation of the sympathetic-immune interface is reviewed with focus on new therapeutic strategies using selective alpha(2)- and beta(2)-adrenoreceptor agonists and antagonists and inhibitors of phosphodiesterase type IV in the treatment of experimental models of autoimmune diseases, fibromyalgia, and chronic fatigue syndrome
2,030 citations
"Stroke-induced immunodeficiency pro..." refers background in this paper
...Catecholamines have been shown to suppress Th1 activities and cellular immune responses either directly, inhibiting the IFN- synthesis by Th1 cells, or indirectly, by inhibition of Th1-polarizing cytokines like IL-12 and TNF- produced by antigen-presenting cells (34)....
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...Instead, catecholamines appear to promote Th2 cell differentiation and cytokine production (34), and trigger the secretion of IL-10 (a potent inhibitor of Th1 and monocyte functions) by monocytes (13)....
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TL;DR: This sales letter may not influence you to be smarter, but the book that the authors offer will evoke you to being smarter and you'll know more than others who don't.
Abstract: This sales letter may not influence you to be smarter, but the book that we offer will evoke you to be smarter. Yeah, at least you'll know more than others who don't. This is what called as the quality life improvisation. Why should this cellular and molecular immunology? It's because this is your favourite theme to read. If you like this theme about, why don't you read the book to enrich your discussion?
1,562 citations
"Stroke-induced immunodeficiency pro..." refers background in this paper
...Because IFN- stimulates the microbicidal activity of phagocytes, whereas IL-4 inhibits phagocytosis, a decreased ratio of IFN- /IL-4 production indicates a compromised antibacterial defense (35)....
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TL;DR: Aspiration pneumonitis (Mendelson's syndrome), whereas aspiration pneumonia is an infectious process caused by the inhalation of oropharyngeal secretions that are colonized by pathogenic bacteria, are distinct clinical entities.
Abstract: Aspiration is defined as the inhalation of oropharyngeal or gastric contents into the larynx and lower respiratory tract.1,2 Several pulmonary syndromes may occur after aspiration, depending on the amount and nature of the aspirated material, the frequency of aspiration, and the host's response to the aspirated material.2 Aspiration pneumonitis (Mendelson's syndrome) is a chemical injury caused by the inhalation of sterile gastric contents, whereas aspiration pneumonia is an infectious process caused by the inhalation of oropharyngeal secretions that are colonized by pathogenic bacteria. Although there is some overlap between these syndromes, they are distinct clinical entities (Table 1). Other . . .
1,246 citations