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Cytokine Jun 2022The interleukin-1 (IL-1) family of cytokines and receptors are implicated in the functioning of innate and adaptive immunity and the genesis of inflammation. They are... (Review)
Review
The interleukin-1 (IL-1) family of cytokines and receptors are implicated in the functioning of innate and adaptive immunity and the genesis of inflammation. They are widely expressed in structural and immune cells with marked expression within barrier mucosal surfaces. In the lung, gut and skin, which are common entry sites for pathogens, they play essential functions in maintaining the functional integrity of the barrier and manage innate and adaptive immunity in response to insult and infections. In tissue sites, the IL-1 cytokines are tightly regulated by mechanisms involving decoy receptors and protease degradation. Dysregulation of these processes are associated with aberrant tissue inflammation leading to a number of inflammatory diseases. This review will address the roles of the different IL-1 cytokines at the lung, gut and skin barrier surfaces at homeostasis, and their roles as inflammatory mediators in diseases such as asthma, chronic obstructive pulmonary disease, inflammatory bowel diseases, atopic dermatitis and psoriasis.
Topics: Adaptive Immunity; Cytokines; Humans; Immunity, Innate; Inflammation; Inflammatory Bowel Diseases; Interleukin-1
PubMed: 35462264
DOI: 10.1016/j.cyto.2022.155890 -
Frontiers in Immunology 2023Interleukin-6 (IL-6) is a key mediator cytokine of the immune response as well as a regulator of many physiological and pathological processes. In Crohn's disease (CD),... (Review)
Review
Interleukin-6 (IL-6) is a key mediator cytokine of the immune response as well as a regulator of many physiological and pathological processes. In Crohn's disease (CD), cytokine imbalance rules the intestinal microenvironment and leads to chronic inflammation of the gut. Pro-inflammatory cytokines are generally upregulated in inflammatory bowel disease (IBD) including TNFα and IL-6. Consequently, drugs that target these cytokines have been long sought and approved. Despite the short-term success in treating CD patients with anti-TNFα, many patients stopped responding to treatment, which made IL-6 an alternative target to alleviate inflammation in these patients. IL-6 has long been approached as part of the therapeutic strategies to treat CD and other inflammatory disorders. Clinical trials of CD patients have targeted IL-6 signaling in different mechanisms: blocking IL-6, neutralizing IL-6 receptor (IL-6R), or trapping the soluble IL-6/IL-6R complex. These trials have faced challenges and side effects in patients with gastrointestinal perforations and ulcers, for example, all of which highlight the dual role of IL-6 during intestinal inflammation and the need for this cytokine for intestinal tissue integrity. IL-6 is involved in a complex of upstream regulators and downstream signaling cascades and maintaining a physiological level of IL-6 in the blood and in the intestine is key for achieving health and homeostasis. In this review, we describe IL-6 biology and signaling and its involvement in intestinal health and inflammation. We also discuss the current strategies for targeting IL-6 pathways in CD patients, as well as molecular regulators representing potential therapeutic targets for IL-6 attenuation.
Topics: Humans; Crohn Disease; Cytokines; Inflammation; Inflammatory Bowel Diseases; Interleukin-6; Tumor Necrosis Factor-alpha
PubMed: 38106420
DOI: 10.3389/fimmu.2023.1295230 -
Frontiers in Immunology 2023Tumor necrosis factor-alpha (TNF-α) is a pleiotropic immune cytokine that belongs to the TNF superfamily of receptor ligands. The cytokine exists as either a... (Review)
Review
Tumor necrosis factor-alpha (TNF-α) is a pleiotropic immune cytokine that belongs to the TNF superfamily of receptor ligands. The cytokine exists as either a transmembrane or a soluble molecule, and targets two distinct receptors, TNF-α receptor 1 (TNFR1) and TNF-α receptor 2 (TNFR2), which activate different signaling cascades and downstream genes. TNF-α cellular responses depend on its molecular form, targeted receptor, and concentration levels. TNF-α plays a multifaceted role in normal physiology that is highly relevant to human health and disease. In the central nervous system (CNS), this cytokine regulates homeostatic functions, such as neurogenesis, myelination, blood-brain barrier permeability and synaptic plasticity. However, it can also potentiate neuronal excitotoxicity and CNS inflammation. The pleiotropism of TNF-α and its various roles in the CNS, whether homeostatic or deleterious, only emphasizes the functional complexity of this cytokine. Anti-TNF-α therapy has demonstrated effectiveness in treating various autoimmune inflammatory diseases and has emerged as a significant treatment option for CNS autoimmune diseases. Nevertheless, it is crucial to recognize that the effects of this therapeutic target are diverse and complex. Contrary to initial expectations, anti-TNF-α therapy has been found to have detrimental effects in multiple sclerosis. This article focuses on describing the various roles, both physiological and pathological, of TNF-α in the CNS. Additionally, it discusses the specific disease processes that are dependent or regulated by TNF-α and the rationale of its use as a therapeutic target.
Topics: Humans; Tumor Necrosis Factor-alpha; Tumor Necrosis Factor Inhibitors; Central Nervous System; Cytokines; Multiple Sclerosis
PubMed: 37483590
DOI: 10.3389/fimmu.2023.1213448 -
Biomolecules Nov 2022Myeloid-derived suppressor cells (MDSCs) are a group of immature and heterogeneous myeloid cells with immunosuppressive functions. MDSCs play important roles in the... (Review)
Review
Myeloid-derived suppressor cells (MDSCs) are a group of immature and heterogeneous myeloid cells with immunosuppressive functions. MDSCs play important roles in the pathogenesis of cancer, chronic inflammatory diseases, and many autoimmune disorders. The accumulation and activation of MDSCs can be regulated by tumor necrosis factor α (TNF-α). In this review, we summarize the roles played by TNF-α in the recruitment, immunosuppressive functions, and chemotaxis of MDSCs, and discuss the potential therapeutic effects of TNF-α upon these cells in tumor growth and some inflammatory disorders.
Topics: Humans; Myeloid-Derived Suppressor Cells; Tumor Necrosis Factor-alpha; Signal Transduction; Autoimmune Diseases; Chemotaxis; Neoplasms
PubMed: 36358977
DOI: 10.3390/biom12111627 -
BMC Pediatrics Apr 2021Childhood-onset systemic lupus erythematosus (cSLE) is a kind of chronic inflammatory disease characterized by a highly abnormal immune system. This study aimed to...
BACKGROUND
Childhood-onset systemic lupus erythematosus (cSLE) is a kind of chronic inflammatory disease characterized by a highly abnormal immune system. This study aimed to detect the serum levels of Th (T helper) cytokines (IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17A, IL-17F, IL-21, IL-22, IFN-γ and TNF-α) in cSLE and healthy controls, and then to elucidate their association with clinical manifestations, disease activity and laboratory parameters. In order to provide clues for early diagnosis and timely intervention treatment of cSLE patients.
METHODS
A total of 33 children with cSLE and 30 healthy children were enrolled in this study. Children in the cSLE group were classified into the inactive or active cSLE group according to their SLE disease activity index 2000 (SLEDAI-2 K) score. Th cytokine profiles in the peripheral blood were detected and analysed.
RESULTS
Levels of IL-2, IL-10 and IL-21 in the cSLE group were significantly higher than those in the healthy control group (P < 0.05, P < 0.01 and P < 0.01, respectively). Expression of IL-2, IL-10 and IL-21 in the active cSLE group was significantly higher than that in the healthy control group (P < 0.05, P < 0.01 and P < 0.05, respectively), but that of IL-22 expression was markedly lower in the active cSLE group than in the healthy control group (P < 0.001). IL-21 in the inactive SLE group was significantly higher than that in the healthy control group (P < 0.05), and levels of IL-2 and IL-10 in the active cSLE group were significantly higher than those in the inactive cSLE group (P < 0.01 and P < 0.05). In-depth analysis showed that after excluding age, gender and drug interference, the levels of IL-2 (P < 0.05), IL-6 (P < 0.05) and IL-10 (P < 0.05) were still positively correlated with SLEDAI-2 K scores. However, the levels of IL-6 (P < 0.05) and IFN- γ (P < 0.05) were still negatively correlated with CD4/CD8, and the concentration of IL-6 (P < 0.05) was still positively correlated with the occurrence of nephritis.
CONCLUSION
This study provides a theoretical basis for the discovery of effective methods to regulate imbalance in T lymphocyte subsets in cSLE, which may lead to new approaches for the diagnosis of cSLE.
Topics: Case-Control Studies; Child; Cytokines; Humans; Lupus Erythematosus, Systemic; Tumor Necrosis Factor-alpha
PubMed: 33882880
DOI: 10.1186/s12887-021-02659-3 -
Advances in Experimental Medicine and... 2020The ability of the immune system to prevent or control the growth of tumor cells is critically dependent on inflammatory processes that lead to the activation,... (Review)
Review
The ability of the immune system to prevent or control the growth of tumor cells is critically dependent on inflammatory processes that lead to the activation, expansion, and recruitment of antitumor effector cells into the tumor microenvironment (TME). These processes are orchestrated by soluble cytokines produced in tissues that alarm local immune surveillance cells (such as dendritic cells, DCs) to mobilize protective antitumor immune populations (B cells, T cells). The interleukin (IL)-36 family of pro-inflammatory cytokines plays an important role in multiple disease processes, ranging from an instigator of autoimmune psoriasis to an initiator of therapeutic immune responses against tumor cells. This chapter will focus on the biologic role of immunomodulatory IL-36 family cytokines in the cancer setting and their potential utility in the design of effective interventional therapies. (127 words).
Topics: Animals; Dendritic Cells; Humans; Interleukin-1; Neoplasms; T-Lymphocytes; Tumor Microenvironment
PubMed: 32060891
DOI: 10.1007/978-3-030-38315-2_8 -
Ear, Nose, & Throat Journal Aug 2022The middle ear bone destruction in chronic otitis media is activated and regulated by inflammation. Chronic otitis media with granulation is a highly active inflammatory...
The middle ear bone destruction in chronic otitis media is activated and regulated by inflammation. Chronic otitis media with granulation is a highly active inflammatory process in which many cytokines are released. The bone is degraded by osteoclasts but, at the same time, protected by cytokines, growth factors, adhesion molecules and osteotropic hormones. Tumor necrosis factor-α, interleukin (IL)-1, IL-6, and OPG/RANKL present in cholesteatoma and granulation accelerate bone lysis and increase the destructive effect on the middle ear.
Topics: Cholesteatoma, Middle Ear; Chronic Disease; Cytokines; Humans; Interleukin-1; Otitis Media; Tumor Necrosis Factor-alpha
PubMed: 33090898
DOI: 10.1177/0145561320955124 -
The Journal of International Medical... Jul 2022To study the association between multi-morbidity percentiles, which is a measure of clinical aging, and interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α.
OBJECTIVES
To study the association between multi-morbidity percentiles, which is a measure of clinical aging, and interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α.
METHODS
Participants 50 to 95 years of age from the Mayo Clinic Study of Aging were assigned age- and sex-specific multi-morbidity percentiles using look-up tables that were reported previously (n = 1646). Percentiles were divided into quintiles for analysis. Plasma IL-6, IL-10, and TNF-α levels were measured in 1595 participants. Median inflammatory marker levels were compared across multi-morbidity quintiles using nonparametric tests.
RESULTS
People with higher multi-morbidity percentiles had significantly higher IL-6 and TNF-α levels compared with those with lower multi-morbidity percentiles. Tests for trend across five multi-morbidity quintiles were significant among women for IL-6 and among participants 70 years of age or older for IL-6 and TNF-α. IL-10 was not associated with multi-morbidity percentiles.
CONCLUSIONS
Multi-morbidity percentiles may be a useful clinical index of biological age for future studies, particularly in women and people 70 years of age and older.
Topics: Aged; Aging; Biological Products; Biomarkers; Female; Humans; Interleukin-6; Male; Multimorbidity; Tumor Necrosis Factor-alpha
PubMed: 35796512
DOI: 10.1177/03000605221109393 -
Journal of the American Chemical Society Oct 2023Coley's toxins, an early and enigmatic form of cancer (immuno)therapy, were based on preparations of . As part of a program to explore bacterial metabolites with...
Coley's toxins, an early and enigmatic form of cancer (immuno)therapy, were based on preparations of . As part of a program to explore bacterial metabolites with immunomodulatory potential, . metabolites were assayed in a cell-based immune assay, and a single membrane lipid, 18:1/18:0/18:1/18:0 cardiolipin, was identified. Its activity was profiled in additional cellular assays, which showed it to be an agonist of a TLR2-TLR1 signaling pathway with a 6 μM EC and robust TNF-α induction. A synthetic analog with switched acyl chains had no measurable activity in immune assays. The identification of a single immunogenic cardiolipin with a restricted structure-activity profile has implications for immune regulation, cancer immunotherapy, and poststreptococcal autoimmune diseases.
Topics: Humans; Streptococcus pyogenes; Cardiolipins; Neoplasms; Tumor Necrosis Factor-alpha
PubMed: 37738205
DOI: 10.1021/jacs.3c07727 -
Biology Direct Sep 2023The thymus is required for T cell development and the formation of the adaptive immunity. Stromal cells, which include thymic epithelial cells (TECs) and mesenchymal...
BACKGROUND
The thymus is required for T cell development and the formation of the adaptive immunity. Stromal cells, which include thymic epithelial cells (TECs) and mesenchymal stromal cells (MSCs), are essential for thymic function. However, the immunomodulatory function of thymus-derived MSCs (T-MSCs) has not been fully explored.
METHODS
MSCs were isolated from mouse thymus and their general characteristics including surface markers and multi-differentiation potential were characterized. The immunomodulatory function of T-MSCs stimulated by IFN-γ and TNF-α was evaluated in vitro and in vivo. Furthermore, the spatial distribution of MSCs in the thymus was interrogated by using tdTomato-flox mice corssed to various MSC lineage Cre recombinase lines.
RESULTS
A subset of T-MSCs express Nestin, and are mainly distributed in the thymic medulla region and cortical-medulla junction, but not in the capsule. The Nestin-positive T-MSCs exhibit typical immunophenotypic characteristics and differentiation potential. Additionally, when stimulated with IFN-γ and TNF-α, they can inhibit activated T lymphocytes as efficiently as BM-MSCs, and this function is dependent on the production of nitric oxide (NO). Additionally, the T-MSCs exhibit a remarkable therapeutic efficacy in acute liver injury and inflammatory bowel disease (IBD).
CONCLUSIONS
Nestin-positive MSCs are mainly distributed in medulla and cortical-medulla junction in thymus and possess immunosuppressive ability upon stimulation by inflammatory cytokines. The findings have implications in understanding the physiological function of MSCs in thymus.
Topics: Animals; Mice; Nestin; Nitric Oxide; Tumor Necrosis Factor-alpha; Mesenchymal Stem Cells; Adaptive Immunity
PubMed: 37723551
DOI: 10.1186/s13062-023-00415-4