scholarly journals The immune system in hypertension

2014 ◽  
Vol 38 (1) ◽  
pp. 20-24 ◽  
Author(s):  
Daniel W. Trott ◽  
David G. Harrison
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Immune System ◽  
Immune Cells ◽  
Cell Activation ◽  
Immune Cell ◽  
Current Evidence ◽  
Interleukin 17 ◽  
Ang Ii ◽  
Immune Cell Activation

While hypertension has predominantly been attributed to perturbations of the vasculature, kidney, and central nervous system, research for almost 50 yr has shown that the immune system also contributes to this disease. Inflammatory cells accumulate in the kidneys and vasculature of humans and experimental animals with hypertension and likely contribute to end-organ damage. We and others have shown that mice lacking adaptive immune cells, including recombinase-activating gene-deficient mice and rats and mice with severe combined immunodeficiency have blunted hypertension to stimuli such as ANG II, high salt, and norepinephrine. Adoptive transfer of T cells restores the blood pressure response to these stimuli. Agonistic antibodies to the ANG II receptor, produced by B cells, contribute to hypertension in experimental models of preeclampsia. The central nervous system seems important in immune cell activation, because lesions in the anteroventral third ventricle block hypertension and T cell activation in response to ANG II. Likewise, genetic manipulation of reactive oxygen species in the subfornical organ modulates both hypertension and immune cell activation. Current evidence indicates that the production of cytokines, including tumor necrosis factor-α, interleukin-17, and interleukin-6, contribute to hypertension, likely via effects on both the kidney and vasculature. In addition, the innate immune system also appears to contribute to hypertension. We propose a working hypothesis linking the sympathetic nervous system, immune cells, production of cytokines, and, ultimately, vascular and renal dysfunction, leading to the augmentation of hypertension. Studies of immune cell activation will clearly be useful in understanding this common yet complex disease.

Aging Leukocytes and the Inflammatory Microenvironment of the Adipose Tissue

Diabetes ◽  
2021 ◽  
Vol 71 (1) ◽  
pp. 23-30
Author(s):  
Korbyn J.V. Dahlquist ◽  
Christina D. Camell
Keyword(s):  
Metabolic Disease ◽  
Adipose Tissue ◽  
Immune System ◽  
Immune Cells ◽  
Cell Activation ◽  
Immune Cell ◽  
Inflammatory Factors ◽  
Immune Cell Activation ◽  
Age Related ◽  
Increased Risk

Age-related immunosenescence, defined as an increase in inflammaging and the decline of the immune system, leads to tissue dysfunction and increased risk for metabolic disease. The elderly population is expanding, leading to a heightened need for therapeutics to improve health span. With age, many alterations of the immune system are observed, including shifts in the tissue-resident immune cells, increased expression of inflammatory factors, and the accumulation of senescent cells, all of which are responsible for a chronic inflammatory loop. Adipose tissue and the immune cell activation within are of particular interest for their well-known roles in metabolic disease. Recent literature reveals that adipose tissue is an organ in which signs of initial aging occur, including immune cell activation. Aged adipose tissue reveals changes in many innate and adaptive immune cell subsets, revealing a complex interaction that contributes to inflammation, increased senescence, impaired catecholamine-induced lipolysis, and impaired insulin sensitivity. Here, we will describe current knowledge surrounding age-related changes in immune cells while relating those findings to recent discoveries regarding immune cells in aged adipose tissue.

scholarly journals Immunomodulation of Epithelium

1996 ◽  
Vol 10 (4) ◽  
pp. 243-248 ◽  
Author(s):  
Mary H Perdue
Keyword(s):  
Mast Cell ◽  
Immune Cells ◽  
Cell Activation ◽  
Immune Cell ◽  
Regulatory System ◽  
Mast Cell Activation ◽  
Immune Cell Activation ◽  
Inflammatory Conditions ◽  
Close Proximity ◽  
Antigenic Material

Many studies have provided evidence that the immune system is a key regulatory system of intestinal function. The interaction of immune cells with the gut epithelium plays an important role in host defence, acting to eliminate pathogens, antigens and other noxious material from the lumen of the gastrointestinal tract. During inflammatory conditions of the gut, the mucosa becomes packed with immune cells in close proximity to the enterocytes. Mediators released from these cells have profound effects on epithelial functions. The two main functions of the intestinal epithelium are to transport nutrients, ions and water, and to act as a barrier to prevent unimpeded uptake of antigenic material and microbes from the lumen. Both these functions are altered by immune reactions in response to various stimuli. Topics discussed include mast cells and epithelial function; mast cell-nerve interaction; mast cell activation; neutrophils, eosinophils and macrophages; T cells; and prostaglandins and immune cell activation.

The attenuation of pain behaviour and serum interleukin-6 concentration by nimesulide in a rat model of neuropathic pain

2010 ◽  
Vol 1 (4) ◽  
pp. 229-234 ◽  
Author(s):  
Taraneh Moini Zanjani ◽  
Masoumeh Sabetkasaei ◽  
Behnaz Karimian ◽  
Farzaneh Labibi ◽  
Babak Farokhi ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neuropathic Pain ◽  
Immune System ◽  
Immune Cells ◽  
Interleukin 6 ◽  
Inflammatory Responses ◽  
Pain Behaviour ◽  
Behavioural Tests

AbstractBackgroundEvidence for a role of immune system in hyperalgesic pain states is increasing. Recent work in neuroimmunology suggests that the immune system does more than simply perform its well known functions of recognizing and removing invading pathogens and tumors. Interest in neuroinflammation and neuroimmune activation has grown rapidly in recent years with the recognition of the role of central nervous system inflammatiom and immune responses in the aetiology of pain states. Among various theories, the role of inflammatory responses of the injured nerve has recently received attention. Cytokines are heterogenous group of polypeptides that activate the immune system and mediate inflammatory responses, acting on a variety of tissue, including the peripheral and central nervous system. Interleukin-6 (IL-6) a pro-inflammatory cytokine, is potentially important in pain aetiology, have pronociceptive actions. Neuropathic pain may be due to a primary insult to the peripheral or central nervous system. Substances released during inflammation from immune cells play an important role in the development and maintenance of chronic pain. Nimesulide, a highly selective cox-2 inhibitor, effectively reduces hyperalgesia due to peripherally administration of inflammatory agents like formalin. The safety of nimesulide was reported for some conditions in which other NSAIDs are contraindicated. Here we have determined the effect of nimesulide on pain behaviour and serum IL-6 level in chronic constriction injury (CCI) model of neuropathic pain.MethodsExperiments were carried out on male Wistar rats, (weight 150–200 g, n = 8). Rats were divided into 3 different groups: 1-CCI + saline 0.9% 2Sham + saline 0.9% (control) 3CCI + drug. Nimesulide (1.25, 2.5, 5 mg/kg, i.p.) was injected 1h before surgery and continued daily to day 14 post-ligation. 42 °C water for thermal hyperalgesia, von Frey filaments for mechanical allodynia, acetone test for cool allodynia and 10 °C water for cold hyperalgesia were respectively used as pain behavioural tests. Behavioural tests were recorded before surgery and on postoperative days 1, 3, 5, 7, 10, 14 and the serum concentration of IL-6 was determined at the day 14.ResultsThe results of this study showed a decrease in hyperalgesia and allodynia following nimesulide administration.ConclusionsIt appears that nimesulide was able to reduce pain behaviour due to nerve inflammation and a parallel decrease in the serum IL-6 concentration was observed.ImplicationsThe immune system is an important mediator in the cascade of events that ultimately results in hyperalgesia. Cytokines contribute to the patheogenesis of neuropathic pain, therefore drugs that inhibit cytokine release from immune cells may reduce inflammatory pain states.

Integrative immunophysiology in the intestinal mucosa

1994 ◽  
Vol 267 (2) ◽  
pp. G151-G165 ◽  
Author(s):  
M. H. Perdue ◽  
D. M. McKay
Keyword(s):  
Immune Cells ◽  
Cell Activation ◽  
Immune Cell ◽  
Intestinal Epithelial ◽  
Immune Cell Activation ◽  
Current State ◽  
Enteric Nerves ◽  
Host Defense Response ◽  
Acid Metabolites ◽  
Epithelial Physiology

Over the past ten years, it has become evident that intestinal epithelial functions such as ion secretion are a host defense response to the presence of antigens, microbes, and other noxious substances in the gut lumen. Such responses are mediated by the activation of immune cells in the mucosa causing release of chemical mediators that act directly or indirectly on the epithelium. Frequently, immune cell products stimulate enteric nerves resulting in amplification. Thus immune cells and nerves form interactive units that can recognize various stimuli both specifically and nonspecifically and initiate mechanisms to eliminate offending material. Here, we review the current state of knowledge regarding immune regulation of epithelial physiology with particular emphasis on the ability of immune cells and their products (biogenic amines, cytokines, arachidonic acid metabolites, oxidants) to alter electrolyte transport. The mast cell will be highlighted in this scheme as this cell has been, and continues to be, the focus of extensive research efforts. However, recently it has become apparent that cells such as lymphocytes, macrophages, and polymorphonuclear leukocytes also play important roles in immunophysiology. The effect of immune cell activation on epithelial functions other than transport, such as permeability, proliferation, and antigen presentation, will be described where appropriate. Finally, we will present evidence that the enterocyte can express an "activated" phenotype and thus participate directly in mucosal immune responses.

scholarly journals Neuroimmune Interactions: From the Brain to the Immune System and Vice Versa

2018 ◽  
Vol 98 (1) ◽  
pp. 477-504 ◽  
Author(s):  
Robert Dantzer
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Immune System ◽  
Long Range ◽  
Immune Cells ◽  
Short Range ◽  
The Body ◽  
Fine Tuning ◽  
Brain Functions ◽  
The Central Nervous System

Because of the compartmentalization of disciplines that shaped the academic landscape of biology and biomedical sciences in the past, physiological systems have long been studied in isolation from each other. This has particularly been the case for the immune system. As a consequence of its ties with pathology and microbiology, immunology as a discipline has largely grown independently of physiology. Accordingly, it has taken a long time for immunologists to accept the concept that the immune system is not self-regulated but functions in close association with the nervous system. These associations are present at different levels of organization. At the local level, there is clear evidence for the production and use of immune factors by the central nervous system and for the production and use of neuroendocrine mediators by the immune system. Short-range interactions between immune cells and peripheral nerve endings innervating immune organs allow the immune system to recruit local neuronal elements for fine tuning of the immune response. Reciprocally, immune cells and mediators play a regulatory role in the nervous system and participate in the elimination and plasticity of synapses during development as well as in synaptic plasticity at adulthood. At the whole organism level, long-range interactions between immune cells and the central nervous system allow the immune system to engage the rest of the body in the fight against infection from pathogenic microorganisms and permit the nervous system to regulate immune functioning. Alterations in communication pathways between the immune system and the nervous system can account for many pathological conditions that were initially attributed to strict organ dysfunction. This applies in particular to psychiatric disorders and several immune-mediated diseases. This review will show how our understanding of this balance between long-range and short-range interactions between the immune system and the central nervous system has evolved over time, since the first demonstrations of immune influences on brain functions. The necessary complementarity of these two modes of communication will then be discussed. Finally, a few examples will illustrate how dysfunction in these communication pathways results in what was formerly considered in psychiatry and immunology to be strict organ pathologies.

Microbiota-immune interactions: from gut to brain

2020 ◽  
Vol 7 (1) ◽  
pp. 1-23 ◽  
Author(s):  
Eloisa Salvo-Romero ◽  
Patricia Stokes ◽  
Mélanie G. Gareau
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Immune System ◽  
Gut Microbiota ◽  
Brain Development ◽  
Immune Cells ◽  
Autism Spectrum ◽  
Immune System Development ◽  
And Function ◽  
The Brain

The vast diversity of bacteria that inhabit the gastrointestinal tract strongly influence host physiology, not only nutrient metabolism but also immune system development and function. The complexity of the microbiota is matched by the complexity of the host immune system, where they have coevolved to maintain homeostasis ensuring the mutualistic host-microbial relationship. Numerous studies in recent years investigating the gut-brain axis have demonstrated an important role for the gut microbiota in modulating brain development and function, with the immune system serving as an important coordinator of these interactions. Gut bacteria can modulate not only gut-resident immune cells but also brain-resident immune cells. Activation of the immune system in the gut and in the brain are implicated in responses to neuroinflammation, brain injury, as well as changes in neurogenesis and plasticity. Impairments in this bidirectional communication are implicated in the etiopathogenesis of psychiatric and neurodevelopmental diseases and disorders, including autism spectrum disorders, or comorbidities associated with Gastrointestinal diseases, including inflammatory bowel diseases, where dysbiosis is commonly seen. Consequently, probiotics, or beneficial microbes, are being recognized as promising therapeutic targets to modulate behavior and brain development by modulating the gut microbiota. Here we review the role of microbiota-immune interactions in the gut and the brain during homeostasis and disease and their impact on gut-brain communication, brain function, and behavior as well as the use of probiotics in central nervous system alterations. Statement of novelty: The microbiota-gut-brain axis is increasingly recognized as an important physiological pathway for maintaining health and impacting the brain and central nervous system. Increasing evidence suggests that the immune system is crucial for gut-brain signaling. In this review, we highlight the critical studies in the literature that identify the key immune pathways involved.

scholarly journals Diabetes Prevention by Immunomodulatory FTY720 Treatment in the LEW.1AR1-iddm Rat Despite Immune Cell Activation

Endocrinology ◽  
2010 ◽  
Vol 151 (8) ◽  
pp. 3555-3565 ◽  
Author(s):  
Anne Jörns ◽  
Klaus Jan Rath ◽  
Taivankhuu Terbish ◽  
Tanja Arndt ◽  
Andreas Meyer zu Vilsendorf ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Proinflammatory Cytokines ◽  
Immune Cells ◽  
Diabetes Prevention ◽  
Cell Activation ◽  
Immune Cell ◽  
Spontaneous Diabetes ◽  
Immune Cell Activation ◽  
Gene And Protein Expression ◽  
Draining Lymph Nodes

The prevention of diabetes by the immunomodulatory agent FTY720 (fingolimod) was studied in the LEW.1AR1-iddm (IDDM) rat, an animal model of human type 1 diabetes. Immune cell subtypes and cytokine profiles in pancreatic islets, secondary lymphoid tissue, and serum were analyzed for signs of immune cell activation. Animals were treated with FTY720 (1 mg/kg body weight) for 40 d starting on d 50 of life. Changes in gene and protein expression of cytokines, CD8 markers, monocyte chemoattractant protein-1, inducible NO synthase, and caspase 3 were evaluated. Treatment with FTY720 prevented diabetes manifestation and islet infiltration around d 60 of life, the usual time of spontaneous diabetes development. On d 120, 30 d after the end of FTY720 therapy, diabetes prevention persisted. However, six of 12 treated animals showed increased gene expression of IL-1β, TNF-α, and CD8 markers in pancreas-draining lymph nodes, indicating immune cell activation. In parallel, serum concentrations of these proinflammatory cytokines were increased. These six animals also showed macrophage infiltration without proinflammatory cytokine expression in a small minority (2–3%) of islets. Interestingly, regulatory T lymphocytes were significantly increased in the efferent vessels of the pancreas-draining lymph nodes only in animals without signs of immune cell activation but not in the rats with immune cell activation. This provides an indication for a lack of protective capacity in the animals with activated immune cells. Thus, FTY720 treatment prevented the manifestation of diabetes by promoting the retention of activated immune cells in the lymph nodes, thereby avoiding islet infiltration and β-cell destruction by proinflammatory cytokines.

scholarly journals Metabolic substrate utilization in stress-induced immune cells

2020 ◽  
Vol 8 (S1) ◽  
Author(s):  
Xiaomin Zhang ◽  
Fabian Zink ◽  
Felix Hezel ◽  
Josef Vogt ◽  
Ulrich Wachter ◽  
...  
Keyword(s):  
Immune Cells ◽  
Metabolic Pathways ◽  
Cell Activation ◽  
Immune Cell ◽  
Tca Cycle ◽  
Therapeutic Interventions ◽  
Functional Changes ◽  
Cell Functions ◽  
Immune Cell Activation ◽  
Metabolic Functions

AbstractImmune cell activation leads to the acquisition of new functions, such as proliferation, chemotaxis, and cytokine production. These functional changes require continuous metabolic adaption in order to sustain ATP homeostasis for sufficient host defense. The bioenergetic demands are usually met by the interconnected metabolic pathways glycolysis, TCA cycle, and oxidative phosphorylation. Apart from glucose, other sources, such as fatty acids and glutamine, are able to fuel the TCA cycle.Rising evidence has shown that cellular metabolism has a direct effect on the regulation of immune cell functions. Thus, quiescent immune cells maintain a basal metabolic state, which shifts to an accelerated metabolic level upon immune cell activation in order to promote key effector functions.This review article summarizes distinct metabolic signatures of key immune cell subsets from quiescence to activation and demonstrates a methodical concept of how to assess cellular metabolic pathways. It further discusses why metabolic functions are of rising interest for translational research and how they can be affected by the underlying pathophysiological condition and/or therapeutic interventions.

scholarly journals Amino acids: key sources for immunometabolites and immunotransmitters

2020 ◽  
Vol 32 (7) ◽  
pp. 435-446 ◽  
Author(s):  
Michio Miyajima
Keyword(s):  
Amino Acids ◽  
Immune Cells ◽  
Nicotinamide Adenine Dinucleotide ◽  
Cell Activation ◽  
Immune Cell ◽  
Nerve Cells ◽  
Metabolic Reprogramming ◽  
Functional Plasticity ◽  
Immune Cell Activation ◽  
Oxide Synthase

Abstract Immune-cell activation and functional plasticity are closely linked to metabolic reprogramming that is required to supply the energy and substrates for such dynamic transformations. During such processes, immune cells metabolize many kinds of molecules including nucleic acids, sugars and lipids, which is called immunometabolism. This review will mainly focus on amino acids and their derivatives among such metabolites and describe the functions of these molecules in the immune system. Although amino acids are essential for, and well known as, substrates for protein synthesis, they are also metabolized as energy sources and as substrates for functional catabolites. For example, glutamine is metabolized to produce energy through glutaminolysis and tryptophan is consumed to supply nicotinamide adenine dinucleotide, whereas arginine is metabolized to produce nitric acid and polyamine by nitric oxide synthase and arginase, respectively. In addition, serine is catabolized to produce nucleotides and to induce methylation reactions. Furthermore, in addition to their intracellular functions, amino acids and their derivatives are secreted and have extracellular functions as immunotransmitters. Many amino acids and their derivatives have been classified as neurotransmitters and their functions are clear as transmitters between nerve cells, or between nerve cells and immune cells, functioning as immunotransmitters. Thus, this review will describe the intracellular and external functions of amino acid from the perspective of immunometabolism and immunotransmission.

scholarly journals Deoxyribonuclease 1-Mediated Clearance of Circulating Chromatin Prevents From Immune Cell Activation and Pro-inflammatory Cytokine Production, a Phenomenon Amplified by Low Trap1 Activity: Consequences for Systemic Lupus Erythematosus

2021 ◽  
Vol 12 ◽  
Author(s):  
Jasmin Felux ◽  
Annika Erbacher ◽  
Magali Breckler ◽  
Roxane Hervé ◽  
Delphine Lemeiter ◽  
...  
Keyword(s):  
Immune Cells ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Immune Cell ◽  
Wild Type ◽  
Systemic Lupus ◽  
Immune Cell Activation ◽  
Deficient Mice

Increased concentrations of circulating chromatin, especially oligo-nucleosomes, are observed in sepsis, cancer and some inflammatory autoimmune diseases like systemic lupus erythematosus (SLE). In SLE, circulating nucleosomes mainly result from increased apoptosis and decreased clearance of apoptotic cells. Once released, nucleosomes behave both as an autoantigen and as a damage-associated molecular pattern (DAMP) by activating several immune cells, especially pro-inflammatory cells. Deoxyribonuclease 1 (DNase1) is a major serum nuclease whose activity is decreased in mouse and human lupus. Likewise, the mitochondrial chaperone tumor necrosis factor (TNF) receptor-associated protein-1 (Trap1) protects against oxidative stress, which is increased in SLE. Here, using wild type, DNase1-deficient and DNase1/Trap1-deficient mice, we demonstrate that DNase1 is a major serum nuclease involved in chromatin degradation, especially when the plasminogen system is activated. In vitro degradation assays show that chromatin digestion is strongly impaired in serum from DNase1/Trap1-deficient mice as compared to wild type mice. In vivo, after injection of purified chromatin, clearance of circulating chromatin is delayed in DNase1/Trap1-deficient mice in comparison to wild type mice. Since defective chromatin clearance may lead to chromatin deposition in tissues and subsequent immune cell activation, spleen cells were stimulated in vitro with chromatin. Splenocytes were activated by chromatin, as shown by interleukin (IL)-12 secretion and CD69 up-regulation. Moreover, cell activation was exacerbated when Trap1 is deficient. Importantly, we also show that cytokines involved in lupus pathogenesis down-regulate Trap1 expression in splenocytes. Therefore, combined low activities of both DNase1 and Trap1 lead to an impaired degradation of chromatin in vitro, delayed chromatin clearance in vivo and enhanced activation of immune cells. This situation may be encountered especially, but not exclusively, in SLE by the negative action of cytokines on Trap1 expression.

Sign in / Sign up

Export Citation Format

Share Document