scholarly journals Cannabis and Inflammatory Mediators

2020 ◽  
Vol 27 (1) ◽  
pp. 16-24
Author(s):  
Marcelo G. Lima ◽  
Vitor S. Tardelli ◽  
Elisa Brietzke ◽  
Thiago M. Fidalgo
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
Inflammatory Response ◽  
Healthy Volunteers ◽  
Inflammatory Mediators ◽  
Inflammatory Markers ◽  
Cannabis Use ◽  
Pubmed Database ◽  
Inflammatory Activation ◽  
The Impact

<b><i>Introduction:</i></b> Although the recreational cannabis use is expressive worldwide, the literature about medical potential of cannabis extracts, including its anti-inflammatory properties, remains inconclusive. <b><i>Methods:</i></b> We screened all articles, published on the PubMed database, on inflammatory mediators and any information about cannabis use from 1980 to March 2019. <b><i>Results:</i></b> Six studies were included, and the main findings were as follows: (i) among healthy volunteers and cannabis users, cannabinoids seemed to decrease the inflammatory response, thus decreasing the immune response, which led to a higher risk of infections; (ii) among patients with multiple sclerosis, cannabinoids seemed to have little impact on the inflammatory markers’ levels. <b><i>Discussion:</i></b> Although cannabis use can produce immune inflammatory suppression in healthy people, this effect is not robust enough to change inflammatory mediators’ levels in situations of highly dysfunctional inflammatory activation. Nevertheless, the impact of cannabinoids in clinical outcomes of these conditions remains to be determined.

scholarly journals Suppression of the Peripheral Immune System Limits the Central Immune Response Following Cuprizone-Feeding: Relevance to Modelling Multiple Sclerosis

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1314 ◽  
Author(s):  
Sen ◽  
Almuslehi ◽  
Gyengesi ◽  
Myers ◽  
Shortland ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
Immune System ◽  
Adaptive Immune System ◽  
Synaptic Function ◽  
Adaptive Immune ◽  
Splenic Atrophy ◽  
The Impact ◽  
The Brain ◽  
Inside Out

Cuprizone (CPZ) preferentially affects oligodendrocytes (OLG), resulting in demyelination. To investigate whether central oligodendrocytosis and gliosis triggered an adaptive immune response, the impact of combining a standard (0.2%) or low (0.1%) dose of ingested CPZ with disruption of the blood brain barrier (BBB), using pertussis toxin (PT), was assessed in mice. 0.2% CPZ(±PT) for 5 weeks produced oligodendrocytosis, demyelination and gliosis plus marked splenic atrophy (37%) and reduced levels of CD4 (44%) and CD8 (61%). Conversely, 0.1% CPZ(±PT) produced a similar oligodendrocytosis, demyelination and gliosis but a smaller reduction in splenic CD4 (11%) and CD8 (14%) levels and no splenic atrophy. Long-term feeding of 0.1% CPZ(±PT) for 12 weeks produced similar reductions in CD4 (27%) and CD8 (43%), as well as splenic atrophy (33%), as seen with 0.2% CPZ(±PT) for 5 weeks. Collectively, these results suggest that 0.1% CPZ for 5 weeks may be a more promising model to study the ‘inside-out’ theory of Multiple Sclerosis (MS). However, neither CD4 nor CD8 were detected in the brain in CPZ±PT groups, indicating that CPZ-mediated suppression of peripheral immune organs is a major impediment to studying the ‘inside-out’ role of the adaptive immune system in this model over long time periods. Notably, CPZ(±PT)-feeding induced changes in the brain proteome related to the suppression of immune function, cellular metabolism, synaptic function and cellular structure/organization, indicating that demyelinating conditions, such as MS, can be initiated in the absence of adaptive immune system involvement.

scholarly journals Microglia: Agents of the CNS Pro-Inflammatory Response

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1717 ◽  
Author(s):  
José A. Rodríguez-Gómez ◽  
Edel Kavanagh ◽  
Pinelopi Engskog-Vlachos ◽  
Mikael K.R. Engskog ◽  
Antonio J. Herrera ◽  
...  
Keyword(s):  
Immune Response ◽  
Inflammatory Response ◽  
Neurodegenerative Diseases ◽  
Current Knowledge ◽  
Reactive Microglia ◽  
Holistic View ◽  
Human Microglia ◽  
Positron Emission ◽  
New Research ◽  
The Impact

The pro-inflammatory immune response driven by microglia is a key contributor to the pathogenesis of several neurodegenerative diseases. Though the research of microglia spans over a century, the last two decades have increased our understanding exponentially. Here, we discuss the phenotypic transformation from homeostatic microglia towards reactive microglia, initiated by specific ligand binding to pattern recognition receptors including toll-like receptor-4 (TLR4) or triggering receptors expressed on myeloid cells-2 (TREM2), as well as pro-inflammatory signaling pathways triggered such as the caspase-mediated immune response. Additionally, new research disciplines such as epigenetics and immunometabolism have provided us with a more holistic view of how changes in DNA methylation, microRNAs, and the metabolome may influence the pro-inflammatory response. This review aimed to discuss our current knowledge of pro-inflammatory microglia from different angles, including recent research highlights such as the role of exosomes in spreading neuroinflammation and emerging techniques in microglia research including positron emission tomography (PET) scanning and the use of human microglia generated from induced pluripotent stem cells (iPSCs). Finally, we also discuss current thoughts on the impact of pro-inflammatory microglia in neurodegenerative diseases.

scholarly journals Fetal inflammation induces acute immune tolerance in the neonatal rat hippocampus

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Garima Singh ◽  
Bradley J. Segura ◽  
Michael K. Georgieff ◽  
Tate Gisslen
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Inflammatory Response ◽  
Immune Tolerance ◽  
Inflammatory Mediators ◽  
Neonatal Rat ◽  
Inflammatory Gene ◽  
Neurocognitive Outcomes ◽  
Tolerance Response ◽  
Nfκb Pathway

Abstract Background Infants born preterm due to chorioamnionitis are frequently affected by a fetal inflammatory response syndrome (FIRS) and then by subsequent postnatal infections. FIRS and postnatal systemic inflammatory events independently contribute to poor neurocognitive outcomes of preterm infants. Developmental integrity of the hippocampus is crucial for intact neurocognitive outcomes in preterms and hippocampally dependent behaviors are particularly vulnerable to preterm systemic inflammation. How FIRS modulates the hippocampal immune response to acute postnatal inflammatory events is not well understood. Methods Prenatal LPS exposed (FIRS) and control neonatal rats received i.p. LPS or saline at postnatal day (P) 5. On P7, immune response was evaluated in the hippocampus of four treatment groups by measuring gene expression of inflammatory mediators and cytosolic and nuclear NFκB pathway proteins. Microglial activation was determined by CD11b+ and Iba1+ immunohistochemistry (IHC) and inflammatory gene expression of isolated microglia. Astrocyte reactivity was measured using Gfap+ IHC. Results Postnatal LPS resulted in a robust hippocampal inflammatory response. In contrast, FIRS induced by prenatal LPS attenuated the response to postnatal LPS exposure, evidenced by decreased gene expression of inflammatory mediators, decreased nuclear NFκB p65 protein, and fewer activated CD11b+ and Iba1+ microglia. Isolated microglia demonstrated inflammatory gene upregulation to postnatal LPS without evidence of immune tolerance by prenatal LPS. Conclusion Prenatal LPS exposure induced immune tolerance to subsequent postnatal LPS exposure in the hippocampus. Microglia demonstrate a robust inflammatory response to postnatal LPS, but only a partial immune tolerance response.

scholarly journals The impact of vitamin D3 intake on inflammatory markers in multiple sclerosis patients and their first-degree relatives

PLoS ONE ◽  
2020 ◽  
Vol 15 (4) ◽  
pp. e0231145 ◽  
Author(s):  
Reza Hashemi ◽  
Seyed Saeed Hosseini-Asl ◽  
Seyed Rafie Arefhosseini ◽  
Mohammad Morshedi
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D3 ◽  
Inflammatory Markers ◽  
First Degree Relatives ◽  
Multiple Sclerosis Patients ◽  
The Impact

scholarly journals Immune Response in Pneumocystis Infections According to the Host Immune System Status

2021 ◽  
Vol 7 (8) ◽  
pp. 625
Author(s):  
Eléna Charpentier ◽  
Sandie Ménard ◽  
Catherine Marques ◽  
Antoine Berry ◽  
Xavier Iriart
Keyword(s):  
Immune Response ◽  
Inflammatory Response ◽  
Immune Status ◽  
Pneumocystis Pneumonia ◽  
Favourable Outcome ◽  
Lung Damage ◽  
Host Immune System ◽  
M1 Macrophage ◽  
Immune Deficiencies ◽  
The Impact

The host immune response is critical in Pneumocystis pneumonia (PCP). Immunocompetent hosts can eliminate the fungus without symptoms, while immunodeficient hosts develop PCP with an unsuitable excessive inflammatory response leading to lung damage. From studies based on rodent models or clinical studies, this review aimed to better understand the pathophysiology of Pneumocystis infection by analysing the role of immune cells, mostly lymphocytes, according to the immune status of the infected host. Hence, this review first describes the immune physiological response in infected immunocompetent hosts that are able to eliminate the fungus. The objective of the second part is to identify the immune elements required for the control of the fungus, focusing on specific immune deficiencies. Finally, the third part concentrates on the effect of the different immune elements in immunocompromised subjects during PCP, to better understand which cells are detrimental, and which, on the contrary, are beneficial once the disease has started. This work highlights that the immune response associated with a favourable outcome of the infection may differ according to the immune status of the host. In the case of immunocompetency, a close communication between B cells and TCD4 within tertiary lymphocyte structures appears critical to activate M2 macrophages without much inflammation. Conversely, in the case of immunodeficiency, a pro-inflammatory response including Th1 CD4, cytotoxic CD8, NK cells, and IFNγ release seems beneficial for M1 macrophage activation, despite the impact of inflammation on lung tissue.

scholarly journals Humoral immune response after COVID-19 in multiple sclerosis: A nation-wide Austrian study

2021 ◽  
pp. 135245852110493
Author(s):  
Gabriel Bsteh ◽  
Sophie Dürauer ◽  
Hamid Assar ◽  
Harald Hegen ◽  
Bettina Heschl ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
Humoral Immune Response ◽  
Antibody Testing ◽  
Seropositivity Rate ◽  
Humoral Immune ◽  
Austrian Study ◽  
Anti Cd20 ◽  
Disease Modifying Treatment ◽  
The Impact

Background: Knowledge on immunity after SARS-CoV-2 infection in patients with multiple sclerosis (pwMS) and the impact of disease-modifying treatment (DMT) is limited. Objective: To evaluate degree, duration and potential predictors of specific humoral immune response in pwMS with prior COVID-19. Methods: Anti-SARS-CoV-2 antibody testing was performed in pwMS with PCR-confirmed diagnosis of symptomatic COVID-19 from a nation-wide registry. Predictors of seropositivity were identified by multivariate regression models. Results: In 125 pwMS (mean age = 42.4 years (SD = 12.3 years), 70% female), anti-SARS-CoV-2 antibodies were detected in 76.0% after a median of 5.2 months from positive PCR. Seropositivity rate was significantly lower in patients on IS-DMT (61.4%, p = 0.001) than without DMT or immunomodulatory DMT (80.6%; 86.0%, respectively). In multivariate analysis, IS-DMT was associated with reduced probability of seropositivity (odds ratio (OR): 0.51; 95% confidence interval (95% CI): 0.17–0.82; p < 0.001). Predefined subgroup analyses showed marked reduction of seropositivity in pwMS on rituximab/ocrelizumab (OR 0.15; 95% CI: 0.05–0.56; p < 0.001). Rate of seropositivity did not change significantly over 6 months. Conclusions: Humoral immunity is stable after SARS-CoV-2 infection in MS, but is reduced by immunosuppressive DMT, particularly anti-CD20 monoclonal antibodies. This provides important evidence for advising pwMS as well as for planning and prioritizing vaccination.

scholarly journals Psychological well-being in people with multiple sclerosis: a descriptive review of the effects obtained with mindfulness interventions

2021 ◽  
Author(s):  
Di Cara Marcella ◽  
Grezzo Denise ◽  
Palmeri Rosanna ◽  
Lo Buono Viviana ◽  
Cartella Emanuele ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Multiple Sclerosis ◽  
Psychological Symptoms ◽  
Positive Impact ◽  
Well Being ◽  
Psychological Well Being ◽  
Pubmed Database ◽  
Mindfulness Interventions ◽  
The Impact

Abstract Multiple sclerosis is a neuroinflammatory and neurodegenerative disease causing several psychosocial problems that significantly impairs quality of life. The most common physical and mental symptoms are anxiety, depression, stress, fatigue, and pain. Several studies investigated the effectiveness of non-pharmacological approaches in improving psychological well-being. This review focused on the impact of mindfulness interventions in patients with multiple sclerosis to reduce psychopathological symptoms and improve well-being. We searched on PubMed database and screening references of included studies and review articles for additional citations. From initial 107 studies, only 8 met search criteria. Our studies showed the efficacy of mindfulness treatment with a reduction in depressive symptoms, a better quality of life (both mental and physical), and a decreased level of fatigue. Findings demonstrated that mindfulness is useful for the improvement of psychological symptoms and pain management and this improvement has also been shown to have a positive impact on the quality of life and coping and adaptation strategies. However, according to the poor available clinics evidence, on cannot conclude that mindfulness interventions are superior to other active interventions in the treatment of psychological symptoms of SM.

scholarly journals Breakthrough SARS-CoV-2 infections after COVID-19 mRNA vaccination in MS patients on disease modifying therapies

2021 ◽  
Author(s):  
Maria Pia Sormani ◽  
Irene Schiavetti ◽  
Matilde Inglese ◽  
Luca Carmisciano ◽  
Alice Laroni ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
Cumulative Incidence ◽  
Vaccine Dose ◽  
Ministry Of Health ◽  
Disease Modifying Therapies ◽  
Disease Modifying ◽  
Antibody Levels ◽  
The Impact

Background. Patients with Multiple Sclerosis (pwMS) treated with anti-CD20 or fingolimod showed a reduced humoral response to mRNA-based SARS-CoV-2 vaccines, while the degree of such responses is unimpaired and similar in pwMS treated with other disease modifying therapies (DMTs), or untreated. However, the nature of the SARS-CoV-2 vaccine-induced immune response is based also on cellular immunity and there is emerging evidence that anti-SARS-CoV-2 specific CD4 and CD8 T cell responses can be detected after vaccination also in patients with low antibody levels. In this study we aimed to monitor the risk of breakthrough SARS-CoV-2 infection and to identify correlates of reduced protection in frail vaccinated pwMS on different DMTs. Methods. We designed a long term clinical follow-up of the CovaXiMS (Covid-19 vaccine in Multiple Sclerosis) , a prospective multicenter cohort study enrolling pwMS scheduled for SARS-CoV-2 vaccination with mRNA vaccines and tested for SARS-CoV-2 antibodies before and after the second vaccine dose. These patients were followed with periodic phone calls up to a mean time of 6 months, and all the SARS-CoV-2 breakthrough infections were registered. The impact of DMTs on cumulative incidence of breakthrough Covid-19 cases was presented by Kaplan-Meier curves. A multivariable logistic model was run to assess factors associated to a higher risk of breakthrough infections. Findings. 1705 pwMS (81.6% BNT162b2 and 18.4% mRNA-1273) had a full vaccination cycle (2 vaccine doses, 21/28 days apart). Of them, 1509 (88.5%) had blood assessment 4 weeks after the second vaccine dose. During follow-up, 23 breakthrough Covid-19 infections (cumulative incidence: 1.5%, SE=0.3%) were detected after a mean of 108 days after the second dose (range, 18-230). Of them, 9 were on ocrelizumab, one on rituximab, 4 on fingolimod, 6 on dimethyl-fumarate, one on teriflunomide, and 2 were untreated. Just two cases (a woman on ocrelizumab and a man on teriflunomide) required hospitalization. The probability to be infected was associated only with SARS-CoV-2 antibody levels measured after 4 weeks from the second vaccine dose (HR=0.63, p=0.007); an antibody level of 660 U/mL was calculated as the cut-off for higher risk of infection. Interpretation. Our data show that the risk of breakthrough SARS-CoV-2 infections is mainly associated with reduced levels of the virus-specific humoral immune response. Funding. FISM [2021/Special-Multi/001]; the Italian Ministry of Health grant Progetto Z844A 5x1000. Italian Ministry of Health: Ricerca Corrente to IRCCS Ospedale Policlinico San Martino.

scholarly journals Effect of different disease-modifying therapies on humoral response to BNT162b2 vaccine in Sardinian multiple sclerosis patients

2021 ◽  
Author(s):  
Maristella Pitzalis ◽  
Maria Laura Idda ◽  
Valeria Lodde ◽  
Annalisa Loizedda ◽  
Monia Lobina ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
Smoking Status ◽  
Humoral Response ◽  
Disease Modifying Therapies ◽  
Significant Difference ◽  
Disease Modifying ◽  
Multiple Sclerosis Patients ◽  
Humoral Responses ◽  
The Impact

Objectives: Vaccination against COVID-19 is highly recommended to patients affected by multiple sclerosis (MS); however, the impact of MS disease-modifying therapies (DMTs) on the immune response following vaccination has been only partially investigated. Here, we aimed to elucidate the effect of DMTs on the humoral immune response to mRNA-based anti-SARS-CoV-2 vaccines in MS patients. Methods: We obtained sera from 912 Sardinian MS patients and 63 healthy controls 30 days after the second dose of BNT162b2 vaccine and tested them for SARS-CoV-2 response using anti-Spike (S) protein-based serology. Previous SARS-CoV-2 infection was assessed by anti-Nucleocapsid (N) serology. Patients were either untreated or undergoing treatment with a total of 13 different DMTs. Differences between treatment groups comprised of at least 10 patients were assessed by generalized linear mixed-effects model. Demographic and clinical data and smoking status were analyzed as additional factors potentially influencing humoral immunity from COVID-19 vaccine. Results: MS patients treated with natalizumab, teriflunomide, azathioprine, fingolimod, ocrelizumab, and rituximab showed significantly lower humoral responses compared to untreated patients. We did not observe a statistically significant difference in response between patients treated with the other drugs (dimethyl fumarate, interferon, alemtuzumab and glatiramer acetate) and untreated patients. In addition, older age, male sex and active smoking were significantly associated with lower antibody titers against SARS-CoV-2. MS patients previously infected with SARS-CoV-2 had significantly higher humoral responses to vaccine than uninfected patients. Conclusion: Humoral response to BNT162b2 is significantly influenced by the specific DMTs followed by patients, as well as by other factors such as previous SARS-CoV-2 infection, age, sex, and smoking status. These results are important to inform targeted strategies to prevent clinically relevant COVID-19 in MS patients.

scholarly journals High Visceral to Subcutaneous Fat Ratio Is Associated with Increased Postoperative Inflammatory Response after Colorectal Resection in Inflammatory Bowel Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Yao Wei ◽  
Feng Zhu ◽  
Jianfeng Gong ◽  
Jianbo Yang ◽  
Tenghui Zhang ◽  
...  
Keyword(s):  
Body Composition ◽  
Colorectal Surgery ◽  
Inflammatory Response ◽  
Inflammatory Markers ◽  
Colorectal Resection ◽  
Univariate Analysis ◽  
Plasma Concentrations ◽  
Subcutaneous Fat ◽  
Infectious Complications ◽  
The Impact

Aim. Excessive postoperative inflammatory response, which is characterized by overproduction of cytokines, often leads to complications after colorectal surgery. However, the impact of body composition on postoperative inflammatory response is largely unknown. The aim of this study is to elucidate whether body fat amount and its distribution affects postoperative inflammation after colorectal surgery in IBD patients. Methods. Eighty-six patients undergoing colorectal resection for IBD from June 2014 to Jan 2017 were enrolled. Abdominal CT images within one week prior to surgery were assessed for visceral fat, subcutaneous fat, and muscle mass. Postoperative inflammatory response was evaluated using serum CRP, PCT, and IL-6 levels on postoperative days 1, 3, and 5. Univariate analysis was conducted to identify risk factors for infectious complications. The correlation between body composition and postoperative plasma concentration of inflammatory markers was analyzed using a linear regression model. ROC curve was applied to analyze the effect of different body composition parameters on postoperative infectious complications and to determine the relationship between inflammatory markers and infectious complications. Results. Neither volume of fat or muscle was related to postoperative plasma concentrations of CRP, IL-6, and PCT. However, visceral to subcutaneous fat ratio was associated with PCT levels on postoperative days (POD) 1, 3, and 5, with the highest regression coefficient on POD1 (β=0.360; 95% CI, 0.089–0.631; P=0.010). Body composition did not predict postoperative infectious complications, while CRP on POD 3 was predictive of infectious complications. Conclusion. Increased visceral to subcutaneous fat ratio was associated with postoperative inflammatory response in IBD patients undergoing colorectal resection. This may partly explain the increased incidence of postoperative complications in patients with visceral obesity.

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