scholarly journals Experimental Cannabinoid 2 Receptor-Mediated Immune Modulation in Sepsis

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
J. Sardinha ◽  
M. E. M. Kelly ◽  
J. Zhou ◽  
C. Lehmann
Keyword(s):  
Immune System ◽  
Receptor Agonist ◽  
Immune Modulation ◽  
Endocannabinoid System ◽  
Systemic Infection ◽  
Great Promise ◽  
Intestinal Microcirculation ◽  
Inflammatory Damage ◽  
Incidence And Mortality ◽  
Adherent Leukocytes

Sepsis is a complex condition that results from a dysregulated immune system in response to a systemic infection. Current treatments lack effectiveness in reducing the incidence and mortality associated with this disease. The endocannabinoid system offers great promise in managing sepsis pathogenesis due to its unique characteristics. The present study explored the effect of modulating the CB2receptor pathway in an acute sepsis mouse model. Endotoxemia was induced by intravenous injection of lipopolysaccharide (LPS) in mice and intestinal microcirculation was assessed through intravital microscopy. We found that HU308 (CB2receptor agonist) reduced the number of adherent leukocytes in submucosal venules but did not restore muscular and mucosal villi FCD in endotoxemic mice. AM630 (CB2receptor antagonist) maintained the level of adherent leukocytes induced by LPS but further reduced muscular and mucosal villi FCD. URB597 (FAAH inhibitor) and JZL184 (MAGL inhibitor) both reduced the number of adherent leukocytes in submucosal venules but did not restore the mucosal villi FCD. Using various compounds we have shown different mechanisms of activating CB2receptors to reduce leukocyte endothelial interactions in order to prevent further inflammatory damage during sepsis.

scholarly journals Infectious and Noninfectious Granulomatosis in Patient with Multiple Sclerosis: Diagnostic Dilemmas and Followup

2014 ◽  
Vol 2014 ◽  
pp. 1-6
Author(s):  
Jelena Paovic ◽  
Predrag Paovic ◽  
Vojislav Sredovic
Keyword(s):  
Multiple Sclerosis ◽  
Immune System ◽  
Pulmonary Tuberculosis ◽  
Cataract Surgery ◽  
Systemic Infection ◽  
Neurological Manifestations ◽  
Initial Attack ◽  
Mri Findings ◽  
Retrobulbar Neuritis ◽  
Preoperative Procedures

Patient was followed up over the course of 30 years. In 1978, after severe systemic infection followed by fever, pulmonary edema, and numerous neurological manifestations, patient was differentially diagnosed with apoplectic form of multiple sclerosis (MS), which was confirmed a year later via neurological and MRI findings. Approximately 20 years following the initial attack, sarcoidosis was diagnosed during the regular preoperative procedures required for cataract surgery. As consequence of lower immune system, infectious granulomatosis in form of pulmonary tuberculosis developed. Ophthalmological findings revealed bilateral retrobulbar neuritis (RBN) approximately six years after initial attack. This developed into total uveitis with retinal periphlebitis and anterior granulomatous uveitis—all of which are clinically similar in both MS and sarcoidosis.

scholarly journals Electrical Stimulation for Immune Modulation in Cancer Treatments

2022 ◽  
Vol 9 ◽  
Author(s):  
Ritopa Das ◽  
Sofia Langou ◽  
Thinh T. Le ◽  
Pooja Prasad ◽  
Feng Lin ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Immune System ◽  
Immune Modulation ◽  
Cancer Treatments ◽  
Different Types ◽  
Specific Antigens ◽  
High Doses ◽  
T Cell Transfer ◽  
Deficient Mice ◽  
Stimulation Of

Immunotherapy is becoming a very common treatment for cancer, using approaches like checkpoint inhibition, T cell transfer therapy, monoclonal antibodies and cancer vaccination. However, these approaches involve high doses of immune therapeutics with problematic side effects. A promising approach to reducing the dose of immunotherapeutic agents given to a cancer patient is to combine it with electrical stimulation, which can act in two ways; it can either modulate the immune system to produce the immune cytokines and agents in the patient’s body or it can increase the cellular uptake of these immune agents via electroporation. Electrical stimulation in form of direct current has been shown to reduce tumor sizes in immune-competent mice while having no effect on tumor sizes in immune-deficient mice. Several studies have used nano-pulsed electrical stimulations to activate the immune system and drive it against tumor cells. This approach has been utilized for different types of cancers, like fibrosarcoma, hepatocellular carcinoma, human papillomavirus etc. Another common approach is to combine electrochemotherapy with immune modulation, either by inducing immunogenic cell death or injecting immunostimulants that increase the effectiveness of the treatments. Several therapies utilize electroporation to deliver immunostimulants (like genes encoded with cytokine producing sequences, cancer specific antigens or fragments of anti-tumor toxins) more effectively. Lastly, electrical stimulation of the vagus nerve can trigger production and activation of anti-tumor immune cells and immune reactions. Hence, the use of electrical stimulation to modulate the immune system in different ways can be a promising approach to treat cancer.

scholarly journals Pathogenesis and Treatment of Cytokine Storm Induced by Infectious Diseases

2021 ◽  
Vol 22 (23) ◽  
pp. 13009
Author(s):  
Xi-Dian Tang ◽  
Tian-Tian Ji ◽  
Jia-Rui Dong ◽  
Hao Feng ◽  
Feng-Qiang Chen ◽  
...  
Keyword(s):  
Immune System ◽  
Infectious Diseases ◽  
Targeted Therapies ◽  
Tissue Damage ◽  
Systemic Infection ◽  
Therapeutic Strategies ◽  
Targeted Treatment ◽  
Cytokine Storm ◽  
Pathophysiological Mechanisms ◽  
Circulating Cytokines

Cytokine storm is a phenomenon characterized by strong elevated circulating cytokines that most often occur after an overreactive immune system is activated by an acute systemic infection. A variety of cells participate in cytokine storm induction and progression, with profiles of cytokines released during cytokine storm varying from disease to disease. This review focuses on pathophysiological mechanisms underlying cytokine storm induction and progression induced by pathogenic invasive infectious diseases. Strategies for targeted treatment of various types of infection-induced cytokine storms are described from both host and pathogen perspectives. In summary, current studies indicate that cytokine storm-targeted therapies can effectively alleviate tissue damage while promoting the clearance of invading pathogens. Based on this premise, “multi-omics” immune system profiling should facilitate the development of more effective therapeutic strategies to alleviate cytokine storms caused by various diseases.

scholarly journals Cannabis, the Endocannabinoid System and Immunity—the Journey from the Bedside to the Bench and Back

2020 ◽  
Vol 21 (12) ◽  
pp. 4448 ◽  
Author(s):  
Osnat Almogi-Hazan ◽  
Reuven Or
Keyword(s):  
Immune Response ◽  
Nervous System ◽  
Immune System ◽  
Immune Surveillance ◽  
Endocannabinoid System ◽  
The Other ◽  
Clinical Use ◽  
Medical Cannabis ◽  
Pathological Conditions ◽  
Regulatory Properties

The Cannabis plant contains numerous components, including cannabinoids and other active molecules. The phyto-cannabinoid activity is mediated by the endocannabinoid system. Cannabinoids affect the nervous system and play significant roles in the regulation of the immune system. While Cannabis is not yet registered as a drug, the potential of cannabinoid-based medicines for the treatment of various conditions has led many countries to authorize their clinical use. However, the data from basic and medical research dedicated to medical Cannabis is currently limited. A variety of pathological conditions involve dysregulation of the immune system. For example, in cancer, immune surveillance and cancer immuno-editing result in immune tolerance. On the other hand, in autoimmune diseases increased immune activity causes tissue damage. Immuno-modulating therapies can regulate the immune system and therefore the immune-regulatory properties of cannabinoids, suggest their use in the therapy of immune related disorders. In this contemporary review, we discuss the roles of the endocannabinoid system in immunity and explore the emerging data about the effects of cannabinoids on the immune response in different pathologies. In addition, we discuss the complexities of using cannabinoid-based treatments in each of these conditions.

Glycan recognition at the interface of the intestinal immune system: Target for immune modulation via dietary components

2011 ◽  
Vol 668 ◽  
pp. S124-S132 ◽  
Author(s):  
Sander de Kivit ◽  
Aletta D. Kraneveld ◽  
Johan Garssen ◽  
Linette E.M. Willemsen
Keyword(s):  
Immune System ◽  
Immune Modulation ◽  
Intestinal Immune System ◽  
Dietary Components

scholarly journals Discovery of Selective Cannabinoid CB2 Receptor Agonists by High-Throughput Screening

2017 ◽  
Vol 23 (4) ◽  
pp. 375-383 ◽  
Author(s):  
Lisa M. Ogawa ◽  
Neil T. Burford ◽  
Yu-Hsien Liao ◽  
Caitlin E. Scott ◽  
Ashley M. Hine ◽  
...  
Keyword(s):  
Side Effects ◽  
High Throughput ◽  
High Throughput Screening ◽  
Immune Modulation ◽  
Cannabinoid Receptors ◽  
Endocannabinoid System ◽  
Allosteric Modulators ◽  
Peripheral Tissues ◽  
Selective Agonists

The endocannabinoid system (ECS) plays a diverse role in human physiology ranging from the regulation of mood and appetite to immune modulation and the response to pain. Drug development that targets the cannabinoid receptors (CB1 and CB2) has been explored; however, success in the clinic has been limited by the psychoactive side effects associated with modulation of the neuronally expressed CB1 that are enriched in the CNS. CB2, however, are expressed in peripheral tissues, primarily in immune cells, and thus development of CB2-selective drugs holds the potential to modulate pain among other indications without eliciting anxiety and other undesirable side effects associated with CB1 activation. As part of a collaborative effort among industry and academic laboratories, we performed a high-throughput screen designed to discover selective agonists or positive allosteric modulators (PAMs) of CB2. Although no CB2 PAMs were identified, 167 CB2 agonists were discovered here, and further characterization of four select compounds revealed two with high selectivity for CB2 versus CB1. These results broaden drug discovery efforts aimed at the ECS and may lead to the development of novel therapies for immune modulation and pain management with improved side effect profiles.

scholarly journals Flea-Borne Transmission Model To Evaluate Vaccine Efficacy against Naturally Acquired Bubonic Plague

2004 ◽  
Vol 72 (4) ◽  
pp. 2052-2056 ◽  
Author(s):  
Clayton O. Jarrett ◽  
Florent Sebbane ◽  
Jeffrey J. Adamovicz ◽  
Gerard P. Andrews ◽  
B. Joseph Hinnebusch
Keyword(s):  
Immune System ◽  
Fusion Protein ◽  
Vaccine Efficacy ◽  
Systemic Infection ◽  
Transmission Model ◽  
Serological Testing ◽  
Protein Vaccine ◽  
Bubonic Plague ◽  
Unvaccinated Control ◽  
New Vaccines

ABSTRACT A flea-to-mouse transmission model was developed for use in testing new candidate vaccines for the ability to protect against flea-borne plague. The model was used to evaluate a recombinant fusion protein vaccine consisting of the Yersinia pestis F1 and V antigens. After one to three challenges with Y. pestis-infected fleas, 14 of 15 unvaccinated control mice developed plague, with an average septicemia level of 9.2 × 108 Y. pestis CFU/ml. None of 15 vaccinated mice developed the disease after similar challenges, and serological testing indicated that transmitted bacteria were eliminated by the immune system before extensive replication and systemic infection could occur. The transmission and development of disease in control mice correlated with the number of bites by blocked fleas but not with the total number of fleabites. The model provides a means to directly assess the efficacy of new vaccines to prevent naturally acquired bubonic plague and to study events at the vector-host interface that lead to dissemination and disease.

β-Glycosphingolipids improve glucose intolerance and hepatic steatosis of the Cohen diabetic rat

2009 ◽  
Vol 296 (1) ◽  
pp. E72-E78 ◽  
Author(s):  
Ehud Zigmond ◽  
Sarah W. Zangen ◽  
Orit Pappo ◽  
Miriam Sklair-Levy ◽  
Gadi Lalazar ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Immune System ◽  
Glucose Tolerance ◽  
Immune Modulation ◽  
Cell Function ◽  
Liver Steatosis ◽  
Diabetic Rat ◽  
Oral Glucose ◽  
Dependent Manner ◽  
Mri Imaging

A link between altered levels of various gangliosides and the development of insulin resistance was described in transgenic mice. Naturally occurring glycosphingolipids were shown to exert immunomodulatory effects in a natural killer T (NKT) cell-dependent manner. This study examined whether glycosphingolipid-induced modulation of the immune system may reduce pancreatic and liver steatosis and stimulate insulin secretion in the Cohen diabetes-sensitive (CDS) rat, a lean model of non-insulin-resistant, nutritionally induced diabetes. Four groups of CDS rats fed a diabetogenic diet were treated with daily intraperitoneal injections of glycosphingolipids β-glucosylceramide, β-lactosylceramide, a combination of both (IGL), or vehicle (PBS) for up to 45 days. Immune modulation was assessed by fluorescence-activated cell sorting analysis of intrahepatic and intrasplenic lymphocytes. Steatosis was assessed by MRI imaging and histological examination of liver and pancreas, Blood glucose and plasma insulin concentrations were assessed during an oral glucose tolerance test. Administration of glycosphingolipids, particularly IGL, increased intrahepatic trapping of CD8 T and NKT lymphocytes. Pancreatic and liver histology were markedly improved and steatosis was reduced in all treated groups compared with vehicle-treated rats. Insulin secretion was restored after glycosphingolipid treatment, resulting in improved glucose tolerance. The immunomodulatory effect of β-glycosphingolipids improved the β-cell function of the hyperglycemic CDS rat. Thus our results suggest a role for the immune system in the pathogenesis of diabetes in this model.

scholarly journals Protection from Systemic Candida albicans Infection by Inactivation of the Sts Phosphatases

2014 ◽  
Vol 83 (2) ◽  
pp. 637-645 ◽  
Author(s):  
Shamoon Naseem ◽  
David Frank ◽  
James B. Konopka ◽  
Nick Carpino
Keyword(s):  
Candida Albicans ◽  
Fungal Pathogen ◽  
Fungal Growth ◽  
Systemic Infection ◽  
Content Type ◽  
Host Immune Responses ◽  
Human Fungal Pathogen ◽  
Rapid Induction ◽  
Inflammatory Damage ◽  
Functional Inactivation

The human fungal pathogenCandida albicanscauses invasive candidiasis, characterized by fatal organ failure due to disseminated fungal growth and inflammatory damage. Thesuppressor ofTCRsignaling 1 (Sts-1) and Sts-2 are two homologous phosphatases that negatively regulate signaling pathways in a number of hematopoietic cell lineages, including T lymphocytes, mast cells, and platelets. Functional inactivation of both Sts enzymes leads to profound resistance to systemic infection byC. albicans, such that greater than 80% of mice lacking Sts-1 and -2 survive a dose ofC. albicans(2.5 × 105CFU/mouse) that is uniformly lethal to wild-type mice within 10 days. Restriction of fungal growth within the kidney occurs by 24 h postinfection in the mutant mice. This occurs without induction of a hyperinflammatory response, as evidenced by the decreased presence of leukocytes and inflammatory cytokines that normally accompany the antifungal immune response. Instead, the absence of the Sts phosphatases leads to the rapid induction of a unique immunological environment within the kidney, as indicated by the early induction of a proinflammatory cytokine (CXL10). Mice lacking either Sts enzyme individually display an intermediate lethality phenotype. These observations identify an opportunity to optimize host immune responses toward a deadly fungal pathogen.

scholarly journals The role of andrographolide and its derivative in COVID-19 associated proteins and immune system

2020 ◽  
Author(s):  
Yadu Nandan Dey ◽  
Pukar Khanal ◽  
B. M. Patil ◽  
Manish M. Wanjari ◽  
Bhavana Srivast ◽  
...  
Keyword(s):  
Immune System ◽  
Signaling Pathway ◽  
Immune Modulation ◽  
Killer Cell ◽  
Mapk Signaling ◽  
Binding Energies ◽  
Gene Set Enrichment Analysis ◽  
Spike Protein ◽  
Network Pharmacology ◽  
Receptor Interaction

Abstract Aim: In view of the strong immunomodulatory and antiviral activity of andrographolide and its derivative, the present study aimed to investigate the binding affinities of andrographolide and its derivative 14-deoxy-11,12-didehydroandrographolide with 3 major targets of COVID-19 i.e. 3CLpro, PLpro and spike protein followed by their gene-set enrichment analysis with special reference to immune modulation.Materials and methods: SMILES of the compounds were retrieved from DigepPred database and the proteins identified were queried in STRING to evaluate the protein-protein interaction and modulated pathways were identified concerning the KEGG database. Drug-likeness and ADMET profiles were evaluated using MolSoft and admet SAR 2.0, respectively. Molecular docking was carried using autodock 4.0.Results: Andrographolide and 14-Deoxy-11,12-didehydroandrographolide were predicted to have a high binding affinity with papain-like protease i.e. -6.7 kcal/mol and -6.5 kcal/mol, respectively while they interact with equal binding energies with 3clpro (-6.8 kcal/mol) and spike protein (-6.9 kcal/mol). Network pharmacology analysis revealed that both compounds modulated the immune system through the regulation of chemokine signaling pathway, Rap1 signaling pathway, Cytokine-cytokine receptor interaction, MAPK signaling pathway, NF-kappa B signaling pathway, Rassignaling pathway, p53 signaling pathway, HIF-1 signaling pathway, and Natural killer cell-mediated cytotoxicity. Although the 14-deoxy-11,12-didehydroandrographolide scored higher drug-likeness character, it showed less potency to interaction with targeted proteins of COVID-19.Conclusion: The study suggests the strong interaction of the andrographolide and its derivative 14-deoxy-11,12-didehydroandrographolide against target proteins associated with COVID-19. Further, network pharmacology analysis elucidated the different pathways of immunomodulation. However, clinical research should be conducted to confirm the current findings.

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