scholarly journals Interleukin-1 in the pathogenesis and treatment of inflammatory diseases

Blood ◽  
2011 ◽  
Vol 117 (14) ◽  
pp. 3720-3732 ◽  
Author(s):  
Charles A. Dinarello
Keyword(s):  
Disease Severity ◽  
Inflammatory Diseases ◽  
Interleukin 1 ◽  
Immunosuppressive Drugs ◽  
Autoinflammatory Diseases ◽  
Inflammatory Conditions ◽  
Sustained Reduction ◽  
Anti Inflammatory ◽  
Smoldering Myeloma ◽  
Acute And Chronic Inflammation

Abstract More than any other cytokine family, the IL-1 family of ligands and receptors is primarily associated with acute and chronic inflammation. The cytosolic segment of each IL-1 receptor family member contains the Toll-IL-1-receptor domain. This domain is also present in each Toll-like receptor, the receptors that respond to microbial products and viruses. Since Toll-IL-1-receptor domains are functional for both receptor families, responses to the IL-1 family are fundamental to innate immunity. Of the 11 members of the IL-1 family, IL-1β has emerged as a therapeutic target for an expanding number of systemic and local inflammatory conditions called autoinflammatory diseases. For these, neutralization of IL-1β results in a rapid and sustained reduction in disease severity. Treatment for autoimmune diseases often includes immunosuppressive drugs whereas neutralization of IL-1β is mostly anti-inflammatory. Although some autoinflammatory diseases are due to gain-of-function mutations for caspase-1 activity, common diseases such as gout, type 2 diabetes, heart failure, recurrent pericarditis, rheumatoid arthritis, and smoldering myeloma also are responsive to IL-1β neutralization. This review summarizes acute and chronic inflammatory diseases that are treated by reducing IL-1β activity and proposes that disease severity is affected by the anti-inflammatory members of the IL-1 family of ligands and receptors.

Review of characteristics and analytical methods for determination of indomethacin

2022 ◽  
Vol 41 (1) ◽  
pp. 34-62
Author(s):  
Andrea Dandić ◽  
Katarina Rajkovača ◽  
Marija Jozanović ◽  
Iva Pukleš ◽  
Aleksandar Széchenyi ◽  
...  
Keyword(s):  
Analytical Methods ◽  
High Performance ◽  
Inflammatory Diseases ◽  
Uv Spectroscopy ◽  
Multicomponent System ◽  
Inflammatory Conditions ◽  
First Choice ◽  
Validation Parameters ◽  
Anti Inflammatory

Abstract Nonsteroidal anti-inflammatory drugs (NSAIDs) are the first choice of treatment for rheumatic disorders and other degenerative inflammatory diseases. One of them, indomethacin (INDO), is highlighted in this study. With its analgesic, antipyretic, and anti-inflammatory properties, it is one of the most powerful drugs used in various clinical trials and therapies related to the mechanism of blocking prostaglandin synthesis, thus reducing and eliminating many inflammatory conditions in patients. To ensure the efficacy and safety of this drug in pharmaceutical and clinical use, precise product quality control is required. Such control is performed with routine pharmaceutical analysis using various chemical methods by which INDO is identified as a separate active ingredient in the multicomponent system of a complete pharmaceutical form. In addition, the determination of INDO is important in clinical practice, where its concentration is determined in different biological samples, ensuring better monitoring of a particular therapy. The most commonly used methods for the determination of INDO are high-performance liquid chromatography (37% of developed methods), voltammetry (16% of developed methods), and UV spectroscopy (11% of developed methods). However, each of these methods must provide precise validation parameters. A combination of analytical methods can lead to more precise results and safer application in practice.

Archidendron lucidum Exerts Anti-Inflammatory Effects by Targeting PDK1 in the NF-κB Pathway

2020 ◽  
Vol 48 (02) ◽  
pp. 429-444
Author(s):  
Minkyeong Jo ◽  
Young-Su Yi ◽  
Jae Youl Cho
Keyword(s):  
Signaling Pathway ◽  
Hplc Analysis ◽  
Inflammatory Diseases ◽  
Interleukin 1 ◽  
Inflammatory Activity ◽  
Raw264.7 Cells ◽  
Luciferase Reporter ◽  
No Production ◽  
Pharmacological Activities ◽  
Anti Inflammatory

Pharmacological activities of some Leguminosae family members were reported. Pharmacological activities of Archidendron lucidum, a Leguminosae family member have never been explored. Therefore, this study investigated anti-inflammatory effects of an Archidendron lucidum methanol extract (Al-ME). In this study, anti-inflammatory effects of Al-ME were investigated in LPS-stimulated RAW264.7 cells and HCl/EtOH-induced gastritis mice by MTT assay, nitric oxide (NO) production assay, semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), luciferase reporter assay, and Western blotting. High-performance liquid chromatography (HPLC) analysis identified ethnopharmacological compounds in Al-ME. Al-ME inhibited NO production without cytotoxicity in peritoneal macrophages and RAW264.7 cells stimulated with LPS or Pam3CSK4. Al-ME downregulated mRNA expression of inflammatory genes (inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2)) and pro-inflammatory cytokines (tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]), interleukin-1[Formula: see text] (IL-1[Formula: see text]), and IL-6). Al-ME exerted anti-inflammatory activity in LPS-stimulated RAW264.7 cells by inhibiting nuclear factor-kappa B (NF-[Formula: see text]B) signaling pathway. HPLC analysis identified quercetin, luteolin, and kaempferol as major anti-inflammatory components in Al-ME. Al-ME ameliorated HCl/EtOH-induced gastritis symptoms in mice by suppressing iNOS and IL-6 mRNA expressions and I[Formula: see text]B[Formula: see text] phosphorylation. Therefore, these results suggest that Al-ME exhibited anti-inflammatory activity by targeting NF-[Formula: see text]B signaling pathway, implying that Al-ME could be potent anti-inflammatory medications to prevent and treat inflammatory diseases.

scholarly journals Development of the doctrine of auto-inflammatory diseases in the XXI century

2019 ◽  
Vol 56 ◽  
pp. 5-18 ◽  
Author(s):  
E. S. Fedorov ◽  
S. O. Salugina ◽  
N. N. Kuzmina
Keyword(s):  
Inflammatory Diseases ◽  
Interleukin 1 ◽  
Autoinflammatory Diseases ◽  
Clinical Rheumatology ◽  
Course Assessment ◽  
New Class ◽  
Hereditary Autoinflammatory Diseases ◽  
Relationship Of

The article presents the development of the doctrine of autoinflammatory diseases (AID) in the last decade. Data on interleukin 1, inflammasomes and their role in the development of AID are presented. The paper also contains the data about interferonopathies and, in particular, proteasomal illnesses as a new class of hereditary autoinflammatory diseases. Variety of AID variants, including diseases with the dominance of one system damage (skin, intestines, bones) is shown. Advances in the AID diagnosis and course assessment of are discussed. Relationship of the AID with the problems of fundamental and clinical rheumatology is demonstrated.

scholarly journals Unveiling the Efficacy, Safety, and Tolerability of Anti-Interleukin-1 Treatment in Monogenic and Multifactorial Autoinflammatory Diseases

2019 ◽  
Vol 20 (8) ◽  
pp. 1898 ◽  
Author(s):  
Alessandra Bettiol ◽  
Giuseppe Lopalco ◽  
Giacomo Emmi ◽  
Luca Cantarini ◽  
Maria Letizia Urban ◽  
...  
Keyword(s):  
Observational Studies ◽  
Interleukin 1 ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Clinical Manifestations ◽  
Autoinflammatory Diseases ◽  
Negative Consequences ◽  
Adherence To Treatment ◽  
Appropriate Treatment ◽  
Sustained Reduction

Autoinflammatory diseases (AIDs) are heterogeneous disorders characterized by dysregulation in the inflammasome, a large intracellular multiprotein platform, leading to overproduction of interleukin-1(IL-1)β that plays a predominant pathogenic role in such diseases. Appropriate treatment is crucial, also considering that AIDs may persist into adulthood with negative consequences on patients’ quality of life. IL-1β blockade results in a sustained reduction of disease severity in most AIDs. A growing experience with the human IL-1 receptor antagonist, Anakinra (ANA), and the monoclonal anti IL-1β antibody, Canakinumab (CANA), has also been engendered, highlighting their efficacy upon protean clinical manifestations of AIDs. Safety and tolerability have been confirmed by several clinical trials and observational studies on both large and small cohorts of AID patients. The same treatment has been proposed in refractory Kawasaki disease, an acute inflammatory vasculitis occurring in children before 5 years, which has been postulated to be autoinflammatory for its phenotypical and immunological similarity with systemic juvenile idiopathic arthritis. Nevertheless, minor concerns about IL-1 antagonists have been raised regarding their employment in children, and the development of novel pharmacological formulations is aimed at minimizing side effects that may affect adherence to treatment. The present review summarizes current findings on the efficacy, safety, and tolerability of ANA and CANA for treatment of AIDs and Kawasaki vasculitis with a specific focus on the pediatric setting.

scholarly journals TIRAP in the Mechanism of Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Sajjan Rajpoot ◽  
Kishore K. Wary ◽  
Rachel Ibbott ◽  
Dongfang Liu ◽  
Uzma Saqib ◽  
...  
Keyword(s):  
Immune Responses ◽  
Protein Interactions ◽  
Inflammatory Diseases ◽  
Interleukin 1 ◽  
Adaptor Protein ◽  
Intracellular Signalling ◽  
Tir Domain ◽  
Signalling Molecules ◽  
Inflammatory Conditions ◽  
Signalling Molecule

The Toll-interleukin-1 Receptor (TIR) domain-containing adaptor protein (TIRAP) represents a key intracellular signalling molecule regulating diverse immune responses. Its capacity to function as an adaptor molecule has been widely investigated in relation to Toll-like Receptor (TLR)-mediated innate immune signalling. Since the discovery of TIRAP in 2001, initial studies were mainly focused on its role as an adaptor protein that couples Myeloid differentiation factor 88 (MyD88) with TLRs, to activate MyD88-dependent TLRs signalling. Subsequent studies delineated TIRAP’s role as a transducer of signalling events through its interaction with non-TLR signalling mediators. Indeed, the ability of TIRAP to interact with an array of intracellular signalling mediators suggests its central role in various immune responses. Therefore, continued studies that elucidate the molecular basis of various TIRAP-protein interactions and how they affect the signalling magnitude, should provide key information on the inflammatory disease mechanisms. This review summarizes the TIRAP recruitment to activated receptors and discusses the mechanism of interactions in relation to the signalling that precede acute and chronic inflammatory diseases. Furthermore, we highlighted the significance of TIRAP-TIR domain containing binding sites for several intracellular inflammatory signalling molecules. Collectively, we discuss the importance of the TIR domain in TIRAP as a key interface involved in protein interactions which could hence serve as a therapeutic target to dampen the extent of acute and chronic inflammatory conditions.

scholarly journals Glucocorticoid Therapy in Inflammatory Bowel Disease: Mechanisms and Clinical Practice

2021 ◽  
Vol 12 ◽  
Author(s):  
Stefano Bruscoli ◽  
Marta Febo ◽  
Carlo Riccardi ◽  
Graziella Migliorati
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Leucine Zipper ◽  
Second Generation ◽  
Inflammatory Diseases ◽  
Drug Effects ◽  
Immunosuppressive Drugs ◽  
Depth Analysis ◽  
Inflammatory Bowel ◽  
Anti Inflammatory

Inflammatory bowel disease (IBD) comprises ulcerative colitis (UC) and Crohn’s disease (CD). IBD etiopathology is multifactorial and involves alteration of immune cells and chronic activation of the inflammatory cascade against yet unknown environmental factors that trigger the disease. IBD therapy aims at improving the quality of life and reducing the risk of disease-related complications to avoid the need for surgery. There is no specific cure for IBDs, and the focus of therapy is supportive measures and use of anti-inflammatory and immunosuppressive drugs. Glucocorticoids (GCs) are powerful anti-inflammatory and immunomodulatory agents used to treat many acute and chronic inflammatory diseases. GCs remain basic treatment for moderate-to-severe IBD, but their use is limited by several important adverse drug effects. Topical administration of a second-generation of GCs, such as budesonide and beclomethasone dipropionate (BDP), represents a valid alternative to use of older, systemic GCs. Administration of second-generation GCs shows promisingly high topical activity and less systemic toxicity, but maintenance therapy with these new GCs in IBD patients is associated with multiple adverse effects. In this review, we make a comparative analysis of the efficacy of first-generation and second-generation GCs in IBD treatment. Unraveling GC biology at the molecular level to uncouple their clinical benefits from detrimental effects is important. One approach is to consider new GC mediators, such as glucocorticoid-induced leucine zipper, which may have similar anti-inflammatory properties, but avoids the side effects of GCs. This in-depth analysis can help to improve the development and the clinical outcomes of GC therapies in IBD.

scholarly journals Effects of aqueous and ethanolic extracts of Aegle marmelos (BAEL) leaves on chronic inflammation in rats

2016 ◽  
Vol 9 (2) ◽  
pp. 52-54
Author(s):  
Sharmin Rahman ◽  
Eliza Omar Eva ◽  
Rezaul Quader ◽  
Muqbula Tasrin ◽  
Md Ismail Khan
Keyword(s):  
Chronic Inflammation ◽  
Granuloma Formation ◽  
Aegle Marmelos ◽  
Inflammatory Conditions ◽  
Flower Stem ◽  
Ethanolic Extracts ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Acute And Chronic Inflammation ◽  
Inflammatory Effect

Aegle Marmelos Linn (Rutaceae) is used as ethno medicine against various human ailments. Several curde extracts from various parts (Leaves, flower, stem, root etc) of the plant A. marmelos Linn have shown variable anti-inflammatory effects in acute and chronic inflammation in animal models. The anti-inflammatory effects of A marmelos linn may be of special advantage compared to conventional anti-inflammatory drugs. The present study has therefore been undertaken with the objective to evaluate the anti inflammatory effect of aqueous and ethanolic extracts of A. marmelos leaves, compared to a standard anti-inflammatory drug (indomethacin) in chronic inflammatory conditions. The anti-inflammatory effect was studied in rats using cotton pellet implantation, where granuloma formation was used as an index of chronic inflammation. Aqueous and ethanolic extracts of A. marmelos leaves were given orally for 7 days daily at doses of 100 mg/kg body weight. The percent inhibition of granuloma formation following treatment with aqueous and ethanolic extracts of A. marmelos leaves, and indomethacin compared to control were 16.5%, 25.72%, and 39.37% respectively. The differences were statistically significant (p<0.05 in case of aqueous and ethanolic extracts and p<0.001 in case of indomethacin). The results suggest that in case of chronic inflammation, both aqueous and ethanolic extracts of A. marmelos have significant anti- inflammatory effect. The ethanolic extracts compared to aqueous extract produced greater anti- inflammatory effects.Ibrahim Med. Coll. J. 2015; 9(2): 52-54

scholarly journals Therapeutic Applications of Terpenes on Inflammatory Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
María Luisa Del Prado-Audelo ◽  
Hernán Cortés ◽  
Isaac H. Caballero-Florán ◽  
Maykel González-Torres ◽  
Lidia Escutia-Guadarrama ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Interleukin 1 ◽  
Biological Properties ◽  
Global Perspective ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Anticonvulsant Activities ◽  
Necrosis Factor

In the last decades, the search for natural products with biological applications as alternative treatments for several inflammatory diseases has increased. In this respect, terpenes are a family of organic compounds obtained mainly from plants and trees, such as tea, cannabis, thyme, and citrus fruits like lemon or mandarin. These molecules present attractive biological properties such as analgesic and anticonvulsant activities. Furthermore, several studies have demonstrated that certain terpenes could reduce inflammation symptoms by decreasing the release of pro-inflammatory cytokines for example, the nuclear transcription factor-kappa B, interleukin 1, and the tumor necrosis factor-alpha. Thus, due to various anti-inflammatory drugs provoking side effects, the search and analysis of novel therapeutics treatments are attractive. In this review, the analysis of terpenes’ chemical structure and their mechanisms in anti-inflammatory functions are addressed. Additionally, we present a general analysis of recent investigations about their applications as an alternative treatment for inflammatory diseases. Furthermore, we focus on terpenes-based nanoformulations and employed dosages to offer a global perspective of the state-of-the-art.

scholarly journals Angiogenin Reduces Immune Inflammation via Inhibition of TANK-Binding Kinase 1 Expression in Human Corneal Fibroblast Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Seung Hoon Lee ◽  
Kyoung Woo Kim ◽  
Kyong-Mi Min ◽  
Kyu-Wan Kim ◽  
Soo-Ik Chang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Mrna Expression ◽  
Nuclear Translocation ◽  
Inflammatory Diseases ◽  
Interleukin 1 ◽  
Necrosis Factor Alpha ◽  
Protein Levels ◽  
Immune Mediated ◽  
Chemotactic Protein ◽  
Anti Inflammatory

Angiogenin (ANG) is reportedly multifunctional, with roles in angiogenesis and autoimmune diseases. This protein is involved in the innate immune system and has been implicated in several inflammatory diseases. Although ANG may be involved in the anti-inflammatory response, there is no evidence that it has direct anti-inflammatory effects. In this study we sought to determine whether ANG has an anti-inflammatory effect in human corneal fibroblasts (HCFs) exposed to media containing tumor necrosis factor-alpha (TNF-α). We found that ANG reduced the mRNA expression of interleukin-1 beta (IL-1β), -6, -8 and TNF-αreceptors (TNFR) 1 and 2. In contrast, ANG increased the mRNA expression of IL-4 and -10. Protein levels of TANK-binding kinase 1 (TBK1) were reduced by ANG in HCFs treated with TNF-α. Moreover, ANG diminished the expression of IL-6 and -8 and monocyte chemotactic protein- (MCP-) 1. The protein expression of nuclear factor-κB (NF-κB) was downregulated by ANG treatment. These findings suggest that ANG suppressed the TNF-α-induced inflammatory response in HCFs through inhibition of TBK1-mediated NF-κB nuclear translocation. These novel results are likely to play a significant role in the selection of immune-mediated inflammatory therapeutic targets and may shed light on the pathogenesis of immune-mediated inflammatory diseases.

Molecular mechanisms of the glucocorticoid receptor in steroid therapy – lessons from transgenic mice

2012 ◽  
Vol 3 (3) ◽  
pp. 241-253 ◽  
Author(s):  
Sabine Hübner ◽  
Jan Tuckermann
Keyword(s):  
Side Effects ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Pathological Condition ◽  
Cell Types ◽  
Therapeutic Effects ◽  
Gene Promoters ◽  
Inflammatory Conditions ◽  
Anti Inflammatory ◽  
And Function

AbstractGlucocorticoids (GCs) are potent anti-inflammatory agents that are used to treat chronic inflammatory diseases, allergic conditions, and some cancers. However, their therapeutic effects are hampered by severe side effects, such as muscle weakness, insulin resistance, fat redistribution, and osteoporosis. GCs act on many cell types that express the GC receptor (GR) via several modes of action. One of them includes GR homodimers recognizing binding sequences in the DNA of gene promoters. Another mode involves the modulation of other DNA-bound transcription factors via dimer-independent mechanisms. To what extent these mechanisms contribute to GC-mediated effects is currently being elucidated from analyses of mice with conditional and function-selective mutations of the GR and is summarized in this review. Whether GR homodimerization or its monomer activity is decisive in the therapeutic effectiveness and associated side effects of GCs for the treatment of inflammatory conditions depends on the type of the pathological condition. Thus, the classic criterion for selective GR modulators, discrimination between GR dimer- and GR monomer-dependent protein-protein interaction, will not help in any condition to avoid side effects and maintain anti-inflammatory activity. Rather, novel criteria for selective GR modulators have to be defined that take into consideration the tissue-specific mechanisms of the GR to achieve optimized anti-inflammatory therapies with reduced side effects. In the case of avoiding osteoporosis as a side effect, a first example of such optimized compounds can be provided.

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