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International Journal of Molecular... Dec 2022The IL-1 superfamily of cytokines is a central regulator of immunity and inflammation. The family is composed of 11 cytokines (with agonist, antagonist, and... (Review)
Review
The IL-1 superfamily of cytokines is a central regulator of immunity and inflammation. The family is composed of 11 cytokines (with agonist, antagonist, and anti-inflammatory properties) and 10 receptors, all tightly regulated through decoy receptor, receptor antagonists, and signaling inhibitors. Inflammation not only is an important physiological response against infection and injury but also plays a central role in atherosclerosis development. Several clinical association studies along with experimental studies have implicated the IL-1 superfamily of cytokines and its receptors in the pathogenesis of cardiovascular disease. Here, we summarize the key features of the IL-1 family, its role in immunity and disease, and how it helps shape the development of atherosclerosis.
Topics: Humans; Interleukin-1; Cytokines; Atherosclerosis; Inflammation; Cardiovascular Diseases
PubMed: 36613465
DOI: 10.3390/ijms24010017 -
The Journal of Allergy and Clinical... Mar 2023Systemic autoinflammatory diseases (SAIDs) are caused by aberrant activation of 1 or more inflammatory pathways in an antigen-independent manner. Monogenic forms of... (Review)
Review
Systemic autoinflammatory diseases (SAIDs) are caused by aberrant activation of 1 or more inflammatory pathways in an antigen-independent manner. Monogenic forms of SAIDs typically manifest during childhood, and early treatment is essential to minimize morbidity and mortality. On the basis of the mechanism of disease and the dominant cytokine(s) that propagates inflammation, monogenic SAIDs can be grouped into major categories including inflammasomopathies/disorders of IL-1, interferonopathies, and disorders of nuclear factor-κB and/or aberrant TNF activity. This classification scheme has direct therapeutic relevance given the availability of biologic agents and small-molecule inhibitors that specifically target these pathways. Here, we review the experience of using biologics that target IL-1 and TNF as well as using Janus kinase inhibitors for the treatment of monogenic SAIDs in pediatric patients. We provide an evidence-based guide for the use of these medications and discuss their mechanism of action, safety profile, and strategies for therapeutic monitoring.
Topics: Animals; Humans; Child; Janus Kinase Inhibitors; Biological Products; Simian Acquired Immunodeficiency Syndrome; Cytokines; Hereditary Autoinflammatory Diseases; Interleukin-1
PubMed: 36707349
DOI: 10.1016/j.jaci.2022.12.816 -
Journal of Hematology & Oncology Mar 2023Inflammasomes are macromolecular platforms formed in response to damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns, whose formation... (Review)
Review
Inflammasomes are macromolecular platforms formed in response to damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns, whose formation would cause maturation of interleukin-1 (IL-1) family members and gasdermin D (GSDMD), leading to IL-1 secretion and pyroptosis respectively. Several kinds of inflammasomes detecting different types of dangers have been found. The activation of inflammasomes is regulated at both transcription and posttranscription levels, which is crucial in protecting the host from infections and sterile insults. Present findings have illustrated that inflammasomes are involved in not only infection but also the pathology of tumors implying an important link between inflammation and tumor development. Generally, inflammasomes participate in tumorigenesis, cell death, metastasis, immune evasion, chemotherapy, target therapy, and radiotherapy. Inflammasome components are upregulated in some tumors, and inflammasomes can be activated in cancer cells and other stromal cells by DAMPs, chemotherapy agents, and radiation. In some cases, inflammasomes inhibit tumor progression by initiating GSDMD-mediated pyroptosis in cancer cells and stimulating IL-1 signal-mediated anti-tumor immunity. However, IL-1 signal recruits immunosuppressive cell subsets in other cases. We discuss the conflicting results and propose some possible explanations. Additionally, we also summarize interventions targeting inflammasome pathways in both preclinical and clinical stages. Interventions targeting inflammasomes are promising for immunotherapy and combination therapy.
Topics: Humans; Inflammasomes; Tumor Microenvironment; Interleukin-1; Inflammation
PubMed: 36932407
DOI: 10.1186/s13045-023-01407-7 -
Frontiers in Immunology 2023Clinical studies have suggested a bidirectional association between non-alcoholic steatohepatitis (NASH) and psoriasis, affecting each other's development and severity....
INTRODUCTION
Clinical studies have suggested a bidirectional association between non-alcoholic steatohepatitis (NASH) and psoriasis, affecting each other's development and severity. Here, we explored bidirectional causal linkages between NASH and psoriasis using a murine model.
METHODS
NASH was induced in mice by streptozotocin injection at 2 days of age and by high-fat diet feeding (STAM™ model). Psoriasis was induced by topical application of imiquimod (IMQ) on the ear. The severities of liver damage and psoriatic skin changes were determined using histological analysis. Gene expression in the skin tissues was evaluated using quantitative PCR analysis. Serum cytokine levels were determined using enzyme-linked immunosorbent assay. To examine the innate immune responses of normal human epidermal keratinocytes (NHEKs), the cells were treated with interleukin (IL)-17A, tumor necrosis factor (TNF)-α, and AdipoRon, an adiponectin receptor agonist.
RESULTS AND DISCUSSION
There were no differences in the degree of liver tissue damage (fat deposition, inflammation, and fibrosis) between NASH mice with and those without psoriasis. Conversely, the co-occurrence of NASH significantly augmented psoriatic skin changes, represented by epidermal hyperplasia, in psoriatic mice. Pro-inflammatory cytokines were expressed in the inflamed skin of psoriatic mice, and the expression of genes, especially , , , and , was significantly upregulated by the co-occurrence of NASH. The expression of keratinocyte activation marker genes and was also upregulated by the co-occurrence of NASH. The serum TNF-α and IL-17 levels were increased by the co-occurrence of NASH and psoriasis. The serum adiponectin levels decreased in NASH mice compared with that in non-NASH mice. In NHEK culture, TNF-α and IL-17A synergistically upregulated , , and expression. The upregulated pro-inflammatory gene expression was suppressed by AdipoRon treatment, reflecting the anti-inflammatory capacity of adiponectin.
CONCLUSION
The co-occurrence of NASH exacerbated psoriatic skin changes associated with increased serum inflammatory cytokine levels and decreased serum adiponectin levels. Combined with findings, increased inflammatory cytokine levels and decreased adiponectin levels likely promote innate immune responses in epidermal keratinocytes in psoriatic skin lesions. Overall, therapeutic intervention for co-occurring NASH is essential to achieve a favorable prognosis of psoriasis in clinical practice.
Topics: Humans; Mice; Animals; Adiponectin; Tumor Necrosis Factor-alpha; Disease Models, Animal; Psoriasis; Non-alcoholic Fatty Liver Disease; Cytokines; Interleukin-1
PubMed: 37646025
DOI: 10.3389/fimmu.2023.1214623 -
International Journal of Molecular... Aug 2023Inflammation and fibrosis are key features of proliferative vitreoretinal disorders. We aimed to define the macrophage phenotype and investigate the role of...
Inflammation and fibrosis are key features of proliferative vitreoretinal disorders. We aimed to define the macrophage phenotype and investigate the role of macrophage-myofibroblast transition (MMT) in the contribution to myofibroblast populations present in epiretinal membranes. Vitreous samples from proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR) and nondiabetic control patients, epiretinal fibrovascular membranes from PDR patients and fibrocellular membranes from PVR patients, human retinal Müller glial cells and human retinal microvascular endothelial cells (HRMECs) were studied by ELISA, immunohistochemistry and flow cytometry analysis. Myofibroblasts expressing α-SMA, fibroblast activation protein-α (FAP-α) and fibroblast-specific protein-1 (FSP-1) were present in all membranes. The majority of CD68 monocytes/macrophages co-expressed the M2 macrophage marker CD206. In epiretinal membranes, cells undergoing MMT were identified by co-expression of the macrophage marker CD68 and myofibroblast markers α-SMA and FSP-1. Further analysis revealed that CD206 M2 macrophages co-expressed α-SMA, FSP-1, FAP-α and ß-catenin. Soluble (s) CD206 and sFAP-α levels were significantly higher in vitreous samples from PDR and PVR patients than in nondiabetic control patients. The proinflammatory cytokine TNF-α and the hypoxia mimetic agent cobalt chloride induced upregulation of sFAP-α in culture media of Müller cells but not of HRMECs. The NF-ĸß inhibitor BAY11-7085 significantly attenuated TNF-α-induced upregulation of sFAP-α in Müller cells. Our findings suggest that the process of MMT might contribute to myofibroblast formation in epiretinal membranes, and this transition involved macrophages with a predominant M2 phenotype. In addition, sFAP-α as a vitreous biomarker may be derived from M2 macrophages transitioned to myofibroblasts and from Müller cells.
Topics: Humans; Endothelial Cells; Myofibroblasts; Epiretinal Membrane; Tumor Necrosis Factor-alpha; Eye Diseases; Diabetic Retinopathy; Vitreoretinopathy, Proliferative
PubMed: 37686317
DOI: 10.3390/ijms241713510 -
Pain Research & Management 2024Neurogenic neuroinflammation has a wide role in migraine pathogenesis including the transition from episodic migraine to chronic one. The seed molecule of neurogenic... (Review)
Review
BACKGROUND
Neurogenic neuroinflammation has a wide role in migraine pathogenesis including the transition from episodic migraine to chronic one. The seed molecule of neurogenic neuroinflammation, i.e., the TNF- proinflammatory molecule, has gathered a lot of attention. This pleiotropic cytokine is a classical component of inflammatory soup, secreted by the microglial cell, and promotes a wide range of inflammatory reactions.
AIM
In this review, we aimed to provide a culminating and comprehending glimpse into the TNF- in association with the migraine.
METHOD
A systematic literature survey method with a mixture of keywords was utilized to grasp the different elements that represent the association between TNF- and migraine. . Highlighted the probable involvement of the TNF- with migraine, the complexity of the matter such as activation of NF-KB signaling cascade, autoactivation, sensitization, and increased likelihood of transition cannot be neglected. Being TNF- as a core node, it becomes the factor for linking diseases such as chronic inflammatory disorders, including COVID-19, and also interaction with other genes to develop severe conditions.
CONCLUSION
To this end, TNF- plays a critical role in chronification, and inhibiting its signaling would likely be a crucial strategy for migraine therapy.
Topics: Humans; Tumor Necrosis Factor-alpha; Neuroinflammatory Diseases; Cytokines; Inflammation; Migraine Disorders
PubMed: 38213956
DOI: 10.1155/2024/1377143 -
International Immunopharmacology Oct 2023Rheumatoid arthritis (RA) is a chronic autoimmune disease that occurs mainly in synovial joints, causing synovial inflammation and joint injury. If diagnosed and treated... (Review)
Review
Rheumatoid arthritis (RA) is a chronic autoimmune disease that occurs mainly in synovial joints, causing synovial inflammation and joint injury. If diagnosed and treated in time, the disease can be well controlled. However, in clinical practice, patients often fail to get timely and effective treatment due to misdiagnosis, missed diagnosis, and other reasons, resulting in deterioration of the condition and poor prognosis, seriously affecting the patient's quality of life. So far, the pathogenesis of RA is still unclear. In recent years, it has been found that the imbalance of cytokines plays a vital role in the occurrence and development of RA. Most RA-related cytokines are produced by immune cells, which bind to the specific receptors of effector cells through paracrine and autocrine pathways. The effect of cytokines on inflammation can be divided into pro-inflammatory and anti-inflammatory factors. When the impact of pro-inflammatory factors is more significant than anti-inflammatory factors, the condition of RA will be aggravated, resulting in more inflammatory severe reactions and immune disorders. Interleukin-33 (IL-33) is a new member of the interleukin-1(IL-1) family, and its receptor is suppression of tumorigenicity 2 (ST2). IL-33 plays a vital role in immune diseases such as RA by promoting a series of biochemical reactions in macrophages, mast cells, granulocytes, and other cells. This article aims to summarize the research progress of IL-33 in the pathogenesis of RA in recent years, discuss its role in the pathogenesis of RA, and provide new ideas for the prevention and treatment of RA in the future.
Topics: Humans; Arthritis, Rheumatoid; Cytokines; Inflammation; Interleukin-1; Interleukin-33; Quality of Life
PubMed: 37562293
DOI: 10.1016/j.intimp.2023.110770 -
Experimental Physiology Jul 2023What is the topic of this review? This review focuses on the physiological role of the cytokine interleukin-1β in the CNS. What advances does it highlight?... (Review)
Review
NEW FINDINGS
What is the topic of this review? This review focuses on the physiological role of the cytokine interleukin-1β in the CNS. What advances does it highlight? Traditionally, interleukin-1β is known as a key mediator of inflammation and immunity. This review highlights the more recent findings describing how interleukin-1β signalling is required to maintain homeostasis in the CNS.
ABSTRACT
Since its discovery in the early 1940s, the interleukin-1 (IL-1) cytokine family has been associated primarily with acute and chronic inflammation. The family member IL-1β is produced by different leucocytes, endothelial cells and epithelial cells. This cytokine has been characterized as a key modulator of inflammation and innate immunity because it induces the transcription of several downstream inflammatory genes. More recently, several groups have demonstrated that IL-1β production is also required to maintain homeostasis in several organ systems. This review focuses on providing an overview of the more recently characterized role of IL-1β in the physiology of the CNS. So far, IL-1β signalling has been implicated in neuronal survival, neurite growth, synaptic pruning, synaptic transmission, neuroplasticity and neuroendocrine functions.
Topics: Humans; Cytokines; Endothelial Cells; Inflammation; Inflammation Mediators; Interleukin-1beta; Neurophysiology
PubMed: 37031383
DOI: 10.1113/EP090780 -
International Journal of Molecular... Jan 2024With cardiovascular disease (CVD) being a primary source of global morbidity and mortality, it is crucial that we understand the molecular pathophysiological mechanisms... (Review)
Review
With cardiovascular disease (CVD) being a primary source of global morbidity and mortality, it is crucial that we understand the molecular pathophysiological mechanisms at play. Recently, numerous pro-inflammatory cytokines have been linked to several different CVDs, which are now often considered an adversely pro-inflammatory state. These cytokines most notably include interleukin-6 (IL-6),tumor necrosis factor (TNF)α, and the interleukin-1 (IL-1) family, amongst others. Not only does inflammation have intricate and complex interactions with pathophysiological processes such as oxidative stress and calcium mishandling, but it also plays a role in the balance between tissue repair and destruction. In this regard, pre-clinical and clinical evidence has clearly demonstrated the involvement and dynamic nature of pro-inflammatory cytokines in many heart conditions; however, the clinical utility of the findings so far remains unclear. Whether these cytokines can serve as markers or risk predictors of disease states or act as potential therapeutic targets, further extensive research is needed to fully understand the complex network of interactions that these molecules encompass in the context of heart disease. This review will highlight the significant advances in our understanding of the contributions of pro-inflammatory cytokines in CVDs, including ischemic heart disease (atherosclerosis, thrombosis, acute myocardial infarction, and ischemia-reperfusion injury), cardiac remodeling (hypertension, cardiac hypertrophy, cardiac fibrosis, cardiac apoptosis, and heart failure), different cardiomyopathies as well as ventricular arrhythmias and atrial fibrillation. In addition, this article is focused on discussing the shortcomings in both pathological and therapeutic aspects of pro-inflammatory cytokines in CVD that still need to be addressed by future studies.
Topics: Humans; Cardiovascular Diseases; Cytokines; Heart Diseases; Interleukin-1; Heart Failure; Tumor Necrosis Factor-alpha
PubMed: 38256155
DOI: 10.3390/ijms25021082 -
Current Cardiology Reports Jan 2022We reviewed the contemporary literature and clinical trials to discuss the applications of the interleukin-1 (IL-1) inhibitor rilonacept to treat pericarditis, with... (Review)
Review
PURPOSE OF REVIEW
We reviewed the contemporary literature and clinical trials to discuss the applications of the interleukin-1 (IL-1) inhibitor rilonacept to treat pericarditis, with regards to pathophysiology, pharmacology, efficacy, and safety.
RECENT FINDINGS
Rilonacept is an emerging novel agent for treating recurrent pericarditis, with phase II and III clinical trials recently published. Rilonacept rapidly resolved pericarditis pain and inflammation, markedly reduced recurrent pericarditis episodes, and had few adverse events indicating a high safety profile. Recurrent pericarditis is associated with significant morbidity and unmet need for novel therapies. Inflammasomes and the IL-1 pathways were found to be critical in its pathophysiology, leading to IL-1 inhibitors being developed. The high efficacy and safety of rilonacept for recurrent pericarditis means it could potentially be considered as a second-line therapy ahead of or as an alternative to corticosteroids, and highlight the great promise of targeted immunomodulatory therapy in this field.
Topics: Humans; Inflammasomes; Interleukin-1; Pericarditis; Recombinant Fusion Proteins; Recurrence
PubMed: 34993745
DOI: 10.1007/s11886-021-01621-0