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International Journal of Molecular... Nov 2022Autism spectrum disorder (ASD) is a neurodevelopmental condition with a so far unknown etiology. Increasing evidence suggests that a state of systemic low-grade... (Meta-Analysis)
Meta-Analysis Review
Activation of the Monocyte/Macrophage System and Abnormal Blood Levels of Lymphocyte Subpopulations in Individuals with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis.
Autism spectrum disorder (ASD) is a neurodevelopmental condition with a so far unknown etiology. Increasing evidence suggests that a state of systemic low-grade inflammation may be involved in the pathophysiology of this condition. However, studies investigating peripheral blood levels of immune cells, and/or of immune cell activation markers such as neopterin are lacking and have provided mixed findings. We performed a systematic review and meta-analysis of studies comparing total and differential white blood cell (WBC) counts, blood levels of lymphocyte subpopulations and of neopterin between individuals with ASD and typically developing (TD) controls (PROSPERO registration number: CRD CRD42019146472). Online searches covered publications from 1 January 1994 until 1 March 2022. Out of 1170 publication records identified, 25 studies were finally included. Random-effects meta-analyses were carried out, and sensitivity analyses were performed to control for potential moderators. Results: Individuals with ASD showed a significantly higher WBC count (k = 10, g = 0.29, p = 0.001, I2 = 34%), significantly higher levels of neutrophils (k = 6, g = 0.29, p = 0.005, I2 = 31%), monocytes (k = 11, g = 0.35, p < 0.001, I2 = 54%), NK cells (k = 7, g = 0.36, p = 0.037, I2 = 67%), Tc cells (k = 4, g = 0.73, p = 0.021, I2 = 82%), and a significantly lower Th/Tc cells ratio (k = 3, g = −0.42, p = 0.008, I2 = 0%), compared to TD controls. Subjects with ASD were also characterized by a significantly higher neutrophil-to-lymphocyte ratio (NLR) (k = 4, g = 0.69, p = 0.040, I2 = 90%), and significantly higher neopterin levels (k = 3, g = 1.16, p = 0.001, I2 = 97%) compared to TD controls. No significant differences were found with respect to the levels of lymphocytes, B cells, Th cells, Treg cells, and Th17 cells. Sensitivity analysis suggested that the findings for monocyte and neutrophil levels were robust, and independent of other factors, such as medication status, diagnostic criteria applied, and/or the difference in age or sex between subjects with ASD and TD controls. Taken together, our findings suggest the existence of a chronically (and systemically) activated inflammatory response system in, at least, a subgroup of individuals with ASD. This might have not only diagnostic, but also, therapeutic implications. However, larger longitudinal studies including more homogeneous samples and laboratory assessment methods and recording potential confounding factors such as body mass index, or the presence of comorbid psychiatric and/or medical conditions are urgently needed to confirm the findings.
Topics: Humans; Monocytes; Autism Spectrum Disorder; Neopterin; Leukocytes; Lymphocyte Subsets; Th17 Cells; Macrophages
PubMed: 36430805
DOI: 10.3390/ijms232214329 -
Fundamental & Clinical Pharmacology Apr 2023Macrophage M2 (MP2)-based cell therapy is a novel medicinal treatment for animals with Experimental Autoimmune Encephalomyelitis (EAE) as an experimental model of... (Meta-Analysis)
Meta-Analysis Review
Cell therapy procedure using anti-inflammatory macrophage M2 can potentially reduce Clinical Score in animals with Experimental Autoimmune Encephalomyelitis: A preclinical systematic review and meta-analysis study.
Macrophage M2 (MP2)-based cell therapy is a novel medicinal treatment for animals with Experimental Autoimmune Encephalomyelitis (EAE) as an experimental model of multiple sclerosis (MS). This systematic review and meta-analysis study was designed to assess the overall therapeutic effects of MP2 cell therapy on Clinical Score and motor impairment in EAE-induced animals. All experiments on MP2 cell therapy in animals with EAE were gathered (by October 2, 2022) from English (PubMed, Scopus, WoS, Science Direct, and ISC) and Persian (MagIran and SID) databases. The searching strategy was designed using "Experimental Autoimmune Encephalomyelitis," "Multiple Sclerosis," and "Macrophage M2" keywords. Following primary and secondary screenings, eligible papers were selected based on the PRISMA 2020 guideline, and the study quality was assessed using the Animal Research: Reporting of In Vivo Experiments (ARRIVE) checklist. The difference in means of Clinical Score (score 0-5) as the effect size (ES) was analyzed based on the random effect model (CMA software, v.2). Subgrouping (EAE phases of Onset, Peak, and Recovery) was applied, and I index was used to assess the heterogeneity index. Publication bias and sensitivity indices were also evaluated. P < 0.05 was considered significant, and the confidence interval (CI) was determined 95%. Among 22 gathered papers, medium to high quality studies were selected for meta-analysis. Difference in means, P value, and I for Onset, Peak, and Recovery phases were 0.082 (CI95%: -0.323-0.159, P value: 0.504, I : 67.961%), -0.606 (CI95%: -1.518 to -0.305, P value: 0.192, I : 96.070%), and -1.103 (CI95%: -1.390 to -0.816, P value: 0.000, I : 30.880%), respectively and Overall Effect was found -0.509 (CI95%: -0.689 to -0.328, P value < 0.001). Also, P value (two-tailed) indices for publication bias were 0.366 and 0.583 for Egger's regression intercept and Begg rank correlation, respectively. The P value for sensitivity was detected 0.003. Cell therapy procedure using MP2 can potentially alleviate the Clinical Scores Index and correct the motor defects in Recovery phase of EAE animals. In healthy mice, the brain and myelin surrounding neurons are in a healthy and physiological state (1). To evaluate MS in humans, it is necessary to model this type of disease in animals using EAE procedure through subcutaneous injection of CFA, MOG , MT, and Pert. Thus, inflammation and autoimmunity occur, which finally lead to myelin destruction and motor symptoms (2). By aspiration of progenitor cells available in bone marrow, the MP2 can be isolated and cultured. By activation of these types of cells, a rich collection of MP2 can be prepared for the cell-therapy process (3). After injection through the tail vein or intra-peritoneal procedure, these cells can be located in CNS through crossing from the BBB. They begin their anti-inflammatory activities and help repair the damaged myelin (4). Eventually, the clinical symptoms can be modified considerably, and the animal motor function improves (5). CFA, complete Freund's adjuvant; MOG , myelin oligodendrocyte glycoprotein; MT, Mycobacterium tuberculosis; Pert, pertussis; EAE, Experimental Autoimmune Encephalomyelitis; BM, bone marrow; MP2, macrophage M2; and BBB, blood brain barrier.
Topics: Humans; Mice; Animals; Encephalomyelitis, Autoimmune, Experimental; Multiple Sclerosis; Myelin-Oligodendrocyte Glycoprotein; Anti-Inflammatory Agents; Macrophages; Mice, Inbred C57BL; Peptide Fragments
PubMed: 36300567
DOI: 10.1111/fcp.12844 -
Materials (Basel, Switzerland) Oct 2022Immunomodulatory biomaterials have the potential to stimulate an immune response able to promote constructive and functional tissue remodeling responses as opposed to... (Review)
Review
UNLABELLED
Immunomodulatory biomaterials have the potential to stimulate an immune response able to promote constructive and functional tissue remodeling responses as opposed to persistent inflammation and scar tissue formation. As such, the controlled activation of macrophages and modulation of their phenotype through implant surface modification has emerged as a key therapeutic strategy.
METHODS
Online databases were searched for in vitro studies between January 1991 and June 2020 which examined the effect of titanium implant surface topography on the adherent macrophage phenotype at either the gene or protein level.
RESULTS
Thirty-nine studies were subsequently included for review. Although there was significant heterogeneity between studies, treatment of titanium surfaces increased the surface roughness or hydrophilicity, and hence increased macrophage attachment but decreased cell spreading. Physical coating of the titanium surface also tended to promote the formation of cell clusters. Titanium and titanium-zirconium alloy with a micro- or nano-scale rough topography combined with a hydrophilic surface chemistry were the most effective surfaces for inducing an anti-inflammatory phenotype in adherent macrophages, as indicated by significant changes in cytokine gene expression and or cytokine secretion profiles.
CONCLUSIONS
The published data support the hypothesis that incorporation of specific topographical and physiochemical surface modifications to titanium can modulate the phenotypic response of adherent macrophages.
PubMed: 36295379
DOI: 10.3390/ma15207314 -
Archives of Dermatological Research Apr 2023This is a literature assessment of essential information and current knowledge that pertains to the potential role for cluster of differentiation (CD) 163+ macrophages... (Review)
Review
This is a literature assessment of essential information and current knowledge that pertains to the potential role for cluster of differentiation (CD) 163+ macrophages in different wound healing models, including extremely rapid tissue regeneration for regenerative medicine purposes. We intend to focus on the beneficial strategies that activate macrophage performance in order to advance the CD163 macrophage-based therapy approaches to accelerate wound healing. We conducted an extensive literature search of peer reviewed articles obtained from the PubMed, Google Scholar, Scopus, Web of Science, and Cochrane databases by using the keywords "wound healing, CD163 macrophages, diabetes mellitus, and burn." There were no limitations in terms of publication date. Our search resulted in 300 papers from which 17 articles were screened according to the inclusion criteria. We divided the selected articles into four distinct groups: healthy humans (n = 5); healthy animals (n = 7); humans with diabetes (n = 2); and animals with diabetes (n = 3). CD163 is a biomarker of the M2c macrophage subtype in mammals. Functions of M2c macrophages include angiogenesis, matrix maturation, and phagocytosis, and they activate prior to wounding. M2c produces many cytokines and growth factors, and also contains receptors for numerous cytokines and growth factors. Induction of M2c macrophages from tissue-resident macrophages in the wound bed by a suitable agent, such as delivery of intracellular ATP, appears to induce rapid granulation tissue formation without hypertrophic scarring and significantly reduces the lag time of the wound healing process.
Topics: Animals; Humans; Wound Healing; Macrophages; Biomarkers; Cytokines; Cicatrix, Hypertrophic; Mammals
PubMed: 36283990
DOI: 10.1007/s00403-022-02407-2 -
AIDS (London, England) Sep 2022Both obesity and HIV infection are characterized by a state of chronic inflammation associated with increased morbidity and mortality. This review aims to assess the...
OBJECTIVE
Both obesity and HIV infection are characterized by a state of chronic inflammation associated with increased morbidity and mortality. This review aims to assess the available literature on immune dysregulation in obesity and people with HIV infection (PWH).
DESIGN
A systematic review of peer-reviewed literature.
METHODS
We conducted a systematic literature search of PubMed, Embase, Scopus, and international conference abstracts for articles on the epidemiology of obesity in the general population and in PWH and the pathogenesis of obesity with a focus on inflammation and immune activation.
RESULTS
Of the 631 articles selected after title review, 490 met the inclusion criteria and 90 were included in the final selection. The selected studies highlight the increasing prevalence of obesity in PWH and a substantial role for antiretroviral treatment (ART) in its development. Pathogenesis of obesity and its associated inflammation derives from disturbances in adipose tissue (AT) immune function, focused on T-cell and macrophage function, with a switch to pro-inflammatory immune phenotype and resulting increases in pro-inflammatory chemokines, which contribute to the development of metabolic syndrome. Although dysregulation of these pathways is seen in both obesity and HIV, there remains a lack of human studies on AT inflammation in HIV.
CONCLUSION
Obesity is an emerging comorbidity in PWH, with a substantial overlap in immune dysregulation patterns seen in both conditions. How this immune dysfunction impacts on development of metabolic complications for both obesity and HIV infection, and whether targeting of AT-derived inflammation will improve outcomes in PWH requires further study.
Topics: Anti-Retroviral Agents; HIV Infections; Host-Pathogen Interactions; Humans; Inflammation; Obesity
PubMed: 35979828
DOI: 10.1097/QAD.0000000000003281 -
Frontiers in Immunology 2022The aim of this research is to discuss the research status, hotspots, frontiers and development trends in the field of adult-onset Still's disease (AOSD) based on...
OBJECTIVES
The aim of this research is to discuss the research status, hotspots, frontiers and development trends in the field of adult-onset Still's disease (AOSD) based on bibliometrics and visual analysis by CiteSpace software.
METHODS
The relevant research articles on AOSD from 1921 to 2021 were retrieved from the Scopus database. CiteSpace software was used to form a visual knowledge map and conduct analysis for the countries/regions, journals, authors, keywords, clusters, research hotspots and frontiers of the included articles.
RESULTS
There were 2,373 articles included, and the number of articles published during 1921-2021 is increasing. The country with the highest number of articles published was Japan (355, 14.96%), followed by the United States (329, 13.86%) and France (215, 9.06%). The author with the highest number of publications is Ansell, Barbara M. (30, 1.26%), and the author with the highest co-citation frequency is Yamaguchi, Masaya (703). is the journal with the highest publication frequency. The top five cluster groups were "joint", "differential diagnosis", "prednisolone", "methotrexate" and "macrophage activation syndrome". The diagnosis, treatment and pathogenesis of AOSD form the main research fields, and prognosis and complications are the research hotspots and trends.
CONCLUSIONS
The global research field in AOSD has expanded in the past 100 years. The complications and new pathogenesis of AOSD are hotspots in this field and need further study in the future.
Topics: Bibliometrics; Humans; Macrophage Activation Syndrome; Methotrexate; Prognosis; Still's Disease, Adult-Onset; United States
PubMed: 35924251
DOI: 10.3389/fimmu.2022.950641 -
Frontiers in Immunology 2022Acute kidney injury (AKI) is a renal disease with a high incidence and mortality. Currently, there are no targeted therapeutics for preventing and treating AKI....
Acute kidney injury (AKI) is a renal disease with a high incidence and mortality. Currently, there are no targeted therapeutics for preventing and treating AKI. Macrophages, important players in mammalian immune response, are involved in the multiple pathological processes of AKI. They are dynamically activated and exhibit a diverse spectrum of functional phenotypes in the kidney after AKI. Targeting the mechanisms of macrophage activation significantly improves the outcomes of AKI in preclinical studies. In this review, we summarize the role of macrophages and the underlying mechanisms of macrophage activation during kidney injury, repair, regeneration, and fibrosis and provide strategies for macrophage-targeted therapies.
Topics: Acute Kidney Injury; Animals; Fibrosis; Kidney; Macrophage Activation; Macrophages; Mammals
PubMed: 35911736
DOI: 10.3389/fimmu.2022.934299 -
Frontiers in Immunology 2022The cytokine interleukin (IL)-1 plays a pivotal role in immune-mediated disorders, particularly in autoinflammatory diseases. Targeting this cytokine proved to be...
BACKGROUND
The cytokine interleukin (IL)-1 plays a pivotal role in immune-mediated disorders, particularly in autoinflammatory diseases. Targeting this cytokine proved to be efficacious in treating numerous IL-1-mediated pathologies. Currently, three IL-1 blockers are approved, namely anakinra, canakinumab and rilonacept, and two additional ones are expected to receive approval, namely gevokizumab and bermekimab. However, there is no systematic review on the safety and efficacy of these biologics in treating immune-mediated diseases.
OBJECTIVE
To evaluate safety and efficacy of anakinra, canakinumab, rilonacept, gevokizumab, and bermekimab for the treatment of immune-mediated disorders compared to placebo, standard-of-care treatment or other biologics.
METHODS
The PRISMA checklist guided the reporting of the data. We searched the PubMed database between 1 January 1984 and 31 December 2020 focusing on immune-mediated disorders. Our PubMed literature search identified 7363 articles. After screening titles and abstracts for the inclusion and exclusion criteria and assessing full texts, 75 articles were included in a narrative synthesis.
RESULTS
Anakinra was both efficacious and safe in treating cryopyrin-associated periodic syndromes (CAPS), familial Mediterranean fever (FMF), gout, macrophage activation syndrome, recurrent pericarditis, rheumatoid arthritis (RA), and systemic juvenile idiopathic arthritis (sJIA). Conversely, anakinra failed to show efficacy in graft-versus-host disease, Sjögren's syndrome, and type 1 diabetes mellitus (T1DM). Canakinumab showed efficacy in treating CAPS, FMF, gout, hyper-IgD syndrome, RA, Schnitzler's syndrome, sJIA, and TNF receptor-associated periodic syndrome. However, use of canakinumab in the treatment of adult-onset Still's disease and T1DM revealed negative results. Rilonacept was efficacious and safe for the treatment of CAPS, FMF, recurrent pericarditis, and sJIA. Contrarily, Rilonacept did not reach superiority compared to placebo in the treatment of T1DM. Gevokizumab showed mixed results in treating Behçet's disease-associated uveitis and no benefit when assessed in T1DM. Bermekimab achieved promising results in the treatment of hidradenitis suppurativa.
CONCLUSIONS
This systematic review of IL-1-targeting biologics summarizes the current state of research, safety, and clinical efficacy of anakinra, bermekimab, canakinumab, gevokizumab, and rilonacept in treating immune-mediated disorders.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021228547.
Topics: Arthritis, Juvenile; Arthritis, Rheumatoid; Biological Products; Cryopyrin-Associated Periodic Syndromes; Diabetes Mellitus, Type 1; Familial Mediterranean Fever; Gout; Humans; Immune System Diseases; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Pericarditis
PubMed: 35874710
DOI: 10.3389/fimmu.2022.888392 -
Brain Sciences May 2022: Ever since the discovery of tumor-associated immune cells, there has been growing interest in the understanding of the mechanisms underlying the crosstalk between... (Review)
Review
: Ever since the discovery of tumor-associated immune cells, there has been growing interest in the understanding of the mechanisms underlying the crosstalk between these cells and tumor cells. A "seed and soil" approach has been recently introduced to describe the glioblastoma (GBM) landscape: tumor microenvironments act as fertile "soil" and interact with the "seed" (glial and stem cells compartment). In the following article, we provide a systematic review of the current evidence pertaining to the characterization of glioma-associated macrophages and microglia (GAMs) and microglia and macrophage cells in the glioma tumor microenvironment (TME). An online literature search was launched on PubMed Medline and Scopus using the following research string: "((Glioma associated macrophages OR GAM OR Microglia) AND (glioblastoma tumor microenvironment OR TME))". The last search for articles pertinent to the topic was conducted in February 2022. The search of the literature yielded a total of 349 results. A total of 235 studies were found to be relevant to our research question and were assessed for eligibility. Upon a full-text review, 58 articles were included in the review. The reviewed papers were further divided into three categories based on their focus: (1) Microglia maintenance of immunological homeostasis and protection against autoimmunity; (2) Microglia crosstalk with dedifferentiated and stem-like glioblastoma cells; (3) Microglia migratory behavior and its activation pattern. Aggressive growth, inevitable recurrence, and scarce response to immunotherapies are driving the necessity to focus on the GBM TME from a different perspective to possibly disentangle its role as a fertile 'soil' for tumor progression and identify within it feasible therapeutic targets. Against this background, our systematic review confirmed microglia to play a paramount role in promoting GBM progression and relapse after treatments. The correct and extensive understanding of microglia-glioma crosstalk could help in understanding the physiopathology of this complex disease, possibly opening scenarios for improvement of treatments.
PubMed: 35741603
DOI: 10.3390/brainsci12060718 -
The Journal of Headache and Pain Jun 2022Several preclinical and clinical lines of evidence suggest a role of neuroinflammation in migraine. Neuroimaging offers the possibility to investigate and localize... (Review)
Review
Several preclinical and clinical lines of evidence suggest a role of neuroinflammation in migraine. Neuroimaging offers the possibility to investigate and localize neuroinflammation in vivo in patients with migraine, and to characterize specific inflammatory constituents, such as vascular permeability, and macrophage or microglia activity. Despite all imaging data accumulated on neuroinflammation across the past three decades, an overview of the imaging evidence of neuroinflammation in migraine is still missing.We conducted a systematic review in the Pubmed and Embase databases to evaluate existing imaging data on inflammation in migraine, and to identify gaps in the literature. We included 20 studies investigating migraine without aura (N = 4), migraine with aura (N = 8), both migraine with and without aura (N = 3), or hemiplegic migraine (N = 5).In migraine without aura, macrophage activation was not evident. In migraine with aura, imaging evidence suggested microglial and parameningeal inflammatory activity. Increased vascular permeability was mostly found in hemiplegic migraine, and was atypical in migraine with and without aura. Based on the weight of existing and emerging data, we show that most studies have concentrated on demonstrating increased vascular permeability as a marker of neuroinflammation, with tools that may not have been optimal. In the future, novel, more sensitive techniques, as well as imaging tracers delineating specific inflammatory pathways may further bridge the gap between preclinical and clinical findings.
Topics: Epilepsy; Hemiplegia; Humans; Migraine with Aura; Migraine without Aura; Phenotype
PubMed: 35650524
DOI: 10.1186/s10194-022-01430-y