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European Spine Journal : Official... Jun 2021Macrophages play an important role in mediating damage after Spinal cord injury (SCI) by secreting macrophage migration inhibitory factor (MMIF) as a secondary injury... (Review)
Review
PURPOSE
Macrophages play an important role in mediating damage after Spinal cord injury (SCI) by secreting macrophage migration inhibitory factor (MMIF) as a secondary injury mediator. We aimed to systematically review the role of MMIF as a therapeutic target after traumatic SCI.
METHODS
Our systematic review has been performed according to the PRISMA 2009 Checklist. A systematic search in the scientific databases was carried out for studies published before 20 February 2019 from major databases. Two researchers independently screened titles. The risk of bias of eligible articles was assessed, and data were extracted. Finally, we systematically analyzed and interpreted related data.
RESULTS
785 papers were selected for the title and abstract screening. 12 papers were included for data extraction. Eight animal studies were of high quality and the remaining two were of medium quality. One of the two human studies was of poor quality and the other was of fair quality. MMIF as a pro-inflammatory mediator can cause increased susceptibility to glutamate-related neurotoxicity, increased nitrite production, increased ERK activation, and increased COX2/PGE2 signaling pathway activation and subsequent stimulation of CCL5-related chemotaxis. Two human studies and six animal studies demonstrated that MMIF level increases after SCI. MMIF inhibition might be a potential therapeutic target in SCI by multiple different mechanisms (6/12 studies).
CONCLUSION
Most animal studies demonstrate significant neurologic improvement after administration of MMIF inhibitors, but these inhibitors have not been studied in humans yet. Further clinical trials are need to further understand MMIF inhibitor utility in acute or chronic SCI.
LEVEL OF EVIDENCE I
Diagnostic: individual cross-sectional studies with the consistently applied reference standard and blinding.
Topics: Animals; Cross-Sectional Studies; Humans; Macrophage Migration-Inhibitory Factors; Spinal Cord; Spinal Cord Injuries
PubMed: 33486594
DOI: 10.1007/s00586-021-06718-2 -
Immunology Letters Jul 2020Notch pathway is highly conserved across species and is involved in the regulation of cell differentiation and activity both in embryonic development and adult life....
BACKGROUND
Notch pathway is highly conserved across species and is involved in the regulation of cell differentiation and activity both in embryonic development and adult life. Notch signaling has an important role in the development of hematopoietic stem cells and their differentiation to committed lineages, as well as in the regulation of several non-hematopoietic cell lines.
OBJECTIVE
As Notch signaling has been implicated in various inflammatory and autoimmune diseases, it is of interest to elucidate what role do Notch receptors and ligands have in inflammatory arthritides.
METHODS
We performed a search on the role of Notch receptors (1-4) and Notch ligands Delta-like (DLL) 1, 3, 4 and Jagged (Jag) 1 and 2 in animal models of inflammatory arthritis and most common types of human inflammatory arthritis (rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis). The initial search identified 135 unique articles, of which 24 were ultimately deemed relevant and included in this systematic review.
RESULTS
Overall, identified articles describe roles for Notch ligands and receptors in inflammatory arthritis, with Notch activation resulting in enhanced Th1/17 polarization, osteoclast differentiation, macrophage activation and fibroblast-like synoviocyte proliferation. However, the inhibitory role of Notch signaling, especially by Jag1 is also described.
CONCLUSION
There is evidence that Notch pathway activation affects multiple cell lineages present within the arthritic environment, therefore potentially acting as one of the drivers of disease pathogenesis. Since cell lineage-selective transgenic mouse models and specific Notch receptor inhibitors are becoming increasingly available, it can be expected that future research will evaluate whether Notch signaling components initiate crucial pathogenic impulses and, therefore, present viable therapeutic targets in inflammatory arthritis.
Topics: Animals; Arthritis; Cell Differentiation; Disease Models, Animal; Humans; Inflammation; Intracellular Signaling Peptides and Proteins; Membrane Proteins; Osteoclasts; Receptors, Notch; Serrate-Jagged Proteins; Th1 Cells; Th17 Cells
PubMed: 32325090
DOI: 10.1016/j.imlet.2020.04.010 -
PloS One 2019HIV and pneumonia infections have both been shown to negatively impact lung function. However, evidence of the role of inflammation on lung dysfunction in HIV and...
HIV and pneumonia infections have both been shown to negatively impact lung function. However, evidence of the role of inflammation on lung dysfunction in HIV and pneumonia co-infected individuals remains limited. We aimed to systematically review the association of inflammatory markers and lung abnormalities in HIV and pneumonia co-infected individuals. This systematic review was registered with the International Prospective Register of Systematic Reviews on August 15, 2017 (registration number CRD42017069254) and used 4 databases (Cochrane Central Register of Controlled Trials, PubMed Central, Clinical Trials.gov and Google Scholar). All clinical trial, observational, and comparative studies targeting adult (> 18 years old) populations with HIV, pneumonia, or both, that report on immune response (cytokine, chemokine, or biomarker), and lung abnormality as an outcome were eligible. Data selection, risk of bias and extraction were performed independently by 2 blinded reviewers. Due to heterogeneity among the articles, a qualitative synthesis was performed. Our search strategy identified 4454 articles of which, 7 met our inclusion criteria. All of the studies investigated the ability of circulating biomarkers to predict lung damage in HIV. None of the articles included patients with both HIV and pneumonia, nor pneumonia alone. Markers of inflammation (IL-6, TNF-α, CRP), innate defense (cathelicidin), monocyte and macrophage activation (sCD14, sCD163 and, IL-2sRα), endothelial dysfunction (ET-1) and general immune health (CD4/CD8 ratio) were associated with lung abnormalities in HIV. This review highlights the lack of available information regarding the impact of inflammatory mediators on lung function in HIV and pneumonia populations, therefore opportunities to prevent lung damage with available anti-inflammatory treatment or to investigate new ones still remain.
Topics: HIV; HIV Infections; Humans; Inflammation Mediators; Respiratory System Abnormalities
PubMed: 31830103
DOI: 10.1371/journal.pone.0226347 -
Antimicrobial Agents and Chemotherapy Jan 2015Recently, there has been a renewed interest in the development of new drugs for the treatment of leishmaniasis. This has spurred the need for pharmacodynamic markers to... (Review)
Review
Recently, there has been a renewed interest in the development of new drugs for the treatment of leishmaniasis. This has spurred the need for pharmacodynamic markers to monitor and compare therapies specifically for visceral leishmaniasis, in which the primary recrudescence of parasites is a particularly long-term event that remains difficult to predict. We performed a systematic review of studies evaluating biomarkers in human patients with visceral, cutaneous, and post-kala-azar dermal leishmaniasis, which yielded a total of 170 studies in which 53 potential pharmacodynamic biomarkers were identified. In conclusion, the large majority of these biomarkers constituted universal indirect markers of activation and subsequent waning of cellular immunity and therefore lacked specificity. Macrophage-related markers demonstrate favorable sensitivity and times to normalcy, but more evidence is required to establish a link between these markers and clinical outcome. Most promising are the markers directly related to the parasite burden, but future effort should be focused on optimization of molecular or antigenic targets to increase the sensitivity of these markers. In general, future research should focus on the longitudinal evaluation of the pharmacodynamic biomarkers during treatment, with an emphasis on the correlation of studied biomarkers and clinical parameters.
Topics: Acute-Phase Proteins; Adenosine Deaminase; Antibodies, Protozoan; Antigens, Protozoan; Biomarkers; Cytokines; Humans; Immunity, Cellular; Leishmania donovani; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Macrophages; Membrane Proteins; Treatment Outcome
PubMed: 25367913
DOI: 10.1128/AAC.04298-14 -
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 -
Mediators of Inflammation Oct 2003Allergic inflammatory responses are driven by cells of the immune system that rely on cytokines to regulate the activity of other immune and structural cells. (Review)
Review
BACKGROUND
Allergic inflammatory responses are driven by cells of the immune system that rely on cytokines to regulate the activity of other immune and structural cells.
OBJECTIVE
To review published studies to (1) identify cytokines consistently increased after allergen challenge in atopic patients and (2) investigate temporal variation in cytokine expression.
METHODS
A PUBMED systematic search was used to extract data from studies involving analysis of cytokine expression in fluids or biopsies following in vivo allergen challenge in atopic patients.
RESULTS
Data were extracted from 82 studies. There were no consistent reports of cytokine protein increase in fluids of patients at 0-1 h after challenge. At 4-12 h, the chemokines eotaxin, macrophage inflammatory protein-1alpha, RANTES (regulated on activation normal T cell expressed and secreted) and interleukin (IL)-8 have all been consistently reported to be up-regulated. At 18-24 h after challenge, the lymphokines IL-4, IL-5 and IL-13, as well as the pro-inflammatory cytokines granulocyte-macrophage colony-stimulating factor, tumour necrosis factor-alpha and IL-6 are consistently increased when compared with the respective control value. There were no reports of up-regulation in interferon-gamma protein and mRNA and in IL-2 mRNA.
CONCLUSION
The expression of granulocyte-macrophage colony-stimulating factor is consistently increased in tissues at 4-12 h after challenge. The influence of this cytokine on antigen capture and presentation by dendritic cells should be further investigated. Additionally, allergen challenge studies are needed that investigate the expression of macrophage-derived chemokine and thymus-regulated and activation-regulated chemokine in tissues of atopic patients. Blocking the effects of these lymphocyte-specific chemokines might provide new therapeutic approaches for the control of allergic inflammation.
Topics: Allergens; Cytokines; Humans; Hypersensitivity
PubMed: 14760932
DOI: 10.1080/09629350310001619717 -
Seminars in Arthritis and Rheumatism Dec 2021Adult-onset Still's disease (AOSD) is a rare inflammatory disease, typically characterized by spiking fever, skin rash, and arthralgia or arthritis. Its conventional... (Review)
Review
BACKGROUND
Adult-onset Still's disease (AOSD) is a rare inflammatory disease, typically characterized by spiking fever, skin rash, and arthralgia or arthritis. Its conventional treatment includes NSAIDs and corticosteroids, and DMARDs as second-line therapy. Frequently, IL-1 inhibitors are also required, mainly in patients refractory to traditional therapy. Canakinumab is a monoclonal antibody that binds IL-1β with high affinity and specificity, making it appropriate for therapeutic purposes in AOSD.
OBJECTIVE
The aim of this systematic review was to identify and compile the current data on the efficacy and safety of canakinumab in the treatment of AOSD.
METHODS
Following the guidelines established by the PRISMA statement, we searched Scopus, Web of Science, Pubmed, and Cochrane Library for relevant literature up to March 2021. The inclusion criteria comprised: randomized controlled trials, pooled analyses, observational studies, case series, and case reports.
RESULTS
Seventeen studies published from 2012 to 2021 were evaluated; 11 of these correspond to case series or case reports, four observational studies, one placebo-controlled phase II trial, and one analysis of pooled systemic juvenile idiopathic arthritis data. In general, out of a total of 99 patients, 68.7% of these presented a complete remission of the systemic and arthritic manifestations at the end of the observation period, while 16.2% of the patients showed a partial improvement of the symptoms and the remaining (15.1%) did not show clinical improvement or were excluded. Moreover, 210 adverse events were reported in 69 patients during canakinumab treatment, of which the majority correspond to respiratory tract infections, arthralgia, disease flares, abdominal pain, nausea, and diarrhea, whereas the most common severe adverse events included macrophage activation syndrome and serious infections. Also, a corticosteroid-sparing effect was observed in a large percentage of patients.
CONCLUSION
More studies with solid evidence are needed to support the efficacy of canakinumab in AOSD, although its use is encouraged by the increasing favorable results reported and the efficacy of other IL-1 inhibitors. It was also associated with an acceptable safety profile, similar to expected in IL-1 inhibitor therapy. However, future studies with well-defined endpoints are warranted to examine further the usefulness of canakinumab in AOSD.
Topics: Adult; Antibodies, Monoclonal, Humanized; Arthritis, Juvenile; Humans; Macrophage Activation Syndrome; Still's Disease, Adult-Onset
PubMed: 34493394
DOI: 10.1016/j.semarthrit.2021.08.007 -
Clinical Chemistry and Laboratory... May 2023The SARS-CoV-2 infection is characterized by both systemic and organ hyper-thromboinflammation, with a clinical course ranging from mild up-to critical systemic... (Meta-Analysis)
Meta-Analysis Review
The SARS-CoV-2 infection is characterized by both systemic and organ hyper-thromboinflammation, with a clinical course ranging from mild up-to critical systemic dysfunction and death. In patients with coronavirus disease 2019 (COVID-19) the monocyte/macrophage population is deeply involved as both trigger and target, assuming the value of useful diagnostic/prognostic marker of innate cellular immunity. Several studies correlated morphological and immunophenotypic alterations of circulating monocytes with clinical outcomes in COVID-19 patients, concluding that monocyte distribution width (MDW) may retain clinical value in stratifying the risk of disease worsening. Through an electronic search in Medline and Scopus we performed an updated literature review and meta-analysis aimed to explore the association between increased MDW levels and illness severity in COVID-19 patients, deciphering role(s) and function(s) of monocytes in the harmful network underlining SARS-CoV-2 infection. We found that significantly elevated MDW values were frequently present in COVID-19 patients who developed unfavorable clinical outcomes, compounded by a significant association between monocyte anisocytosis and SARS-CoV-2 outcomes. These findings suggest that blood MDW index and its scatter plot could represent useful routine laboratory tools for early identification of patients at higher risk of unfavorable COVID-19 and for monitoring the progression of viral infection, clinical outcomes, and therapeutic efficacy throughout hospitalization. According to this evidence, therapeutic decisions in patients with SARS-CoV-2 infection could benefit from monitoring MDW value, with administration of drugs limiting thrombo-inflammation due to monocyte hyper-activation in patients with severe/critical COVID-19 disease.
Topics: Humans; COVID-19; Monocytes; SARS-CoV-2; Inflammation; Thrombosis
PubMed: 36626568
DOI: 10.1515/cclm-2022-0936 -
Rheumatology International Jul 2023A literature review on new-onset autoimmune connective tissue diseases (ACTDs) following COVID-19 is lacking. We evaluated potential associations between COVID-19 and...
A literature review on new-onset autoimmune connective tissue diseases (ACTDs) following COVID-19 is lacking. We evaluated potential associations between COVID-19 and the development of new-onset ACTDs. The "population" was adults with disease terms for ACTDs, including systemic lupus erythematosus (SLE), Sjogren's syndrome, systemic sclerosis (SSc), idiopathic inflammatory myositis (IIM), anti-synthetase syndrome, mixed CTD and undifferentiated CTD, and "intervention" as COVID-19 and related terms. Databases were searched for English-language articles published until September 2022. We identified 2236 articles with 28 ultimately included. Of the 28 included patients, 64.3% were female, with a mean age was 51.1 years. The USA reported the most cases (9/28). ACTD diagnoses comprised: 11 (39.3%) IIM (including four dermatomyositis); 7 (25%) SLE; four (14.3%) anti-synthetase syndrome; four (14.3%) SSc; two (7.1%) other ACTD (one lupus/MCTD overlap). Of eight, four (14.3%) patients (including that with lupus/MCTD) had lupus nephritis. The average time from COVID-19 to ACTD diagnosis was 23.7 days. A third of patients were admitted to critical care, one for treatment of haemophagocytic lymphohistiocytosis in SLE (14 sessions of plasmapheresis, rituximab and intravenous corticosteroids) and nine due to COVID-19. 80% of patients went into remission of ACTD following treatment, while three (10%) patients died-one due to macrophage activation syndrome with anti-synthetase syndrome and two from unreported causes. Our results suggest a potential association between COVID-19 and new-onset ACTDs, notably in young females, reflecting more comprehensive CTD epidemiology. The most common diagnosis in our cohort was IIM. The aetiology and mechanisms by which ACTDs emerge following COVID-19 remain unknown and require further research.
Topics: Adult; Humans; Female; Middle Aged; Male; Mixed Connective Tissue Disease; Incidence; COVID-19; Connective Tissue Diseases; Autoimmune Diseases; Lupus Erythematosus, Systemic; Scleroderma, Systemic; Prognosis; Lupus Nephritis; Myositis
PubMed: 36786873
DOI: 10.1007/s00296-023-05283-9 -
European Review For Medical and... Oct 2012Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome that is often fatal despite treatment. It is caused by a dysregulation in natural killer T-cell function,... (Review)
Review
BACKGROUND
Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome that is often fatal despite treatment. It is caused by a dysregulation in natural killer T-cell function, resulting in activation and proliferation of histiocytes with uncontrolled hemophagocytosis and cytokines overproduction. The syndrome is characterized by fever, hepatosplenomegaly, cytopenias, liver dysfunction, and hyperferritinemia. HLH can be either primary, with a genetic aetiology, or secondary, associated with malignancies, autoimmune diseases, or infections.
AIM
To focus on secondary HLH complicating zoonotic diseases.
MATERIALS AND METHODS
PubMed search of human cases of HLH occurring during zoonotic diseases was performed combining the terms (haemophagocytic or haemophagocytosis or hemophagocytosis or hemophagocytic or erythrophagocytosis or macrophage activation syndrome) with each one of the etiological agents of zoonoses.
RESULTS
Among bacterial diseases, most papers reported cases occurring during brucellosis, rickettsial diseases and Q fever. Regarding viral diseases, most of the cases were reported in patients with avian influenza A subtype H5N1. Among the protozoan zoonoses, most of the cases were reported in patients with visceral leishmaniasis. Regarding zoonotic fungi, most of the cases were reported in AIDS patient with histoplasmosis. No cases of secondary HLH were reported in patient with zoonotic helminthes.
CONCLUSIONS
Zoonotic diseases are an important cause of HLH. Secondary HLH can delay the correct diagnosis of the zoonotic disease, and can contribute to an adverse outcome.
Topics: Animals; Comorbidity; Humans; Lymphohistiocytosis, Hemophagocytic; Zoonoses
PubMed: 23104648
DOI: No ID Found