ArticleArthritis research & therapy2018
NLRP3 inflammasome inhibitor OLT1177 suppresses joint inflammation in murine models of acute arthritis.
Article in Arthritis research & therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers, 1 of them a synthesis that pooled it.
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Who cites it
99 citing papers in PubMed, 1 synthesis or guideline pooled it, 157 citations in OpenAlex.
- Role of NLRP3 in the pathogenesis and treatment of gout arthritis.Frontiers in immunology · 2023Pooled it
- Nano-curcumin therapy, a promising method in modulating inflammatory cytokines in COVID-19 patients.International immunopharmacology · 2020Trial
- Management of Musculoskeletal Injuries with an Inflammatory Damage-Associated Molecular Pattern (DAMP) Etiology.Pain and therapy · 2026Review
- NLRP3 Regulation in Neonatal Hypoxic-Ischemic Encephalopathy-Focus on Microglial Activation.International journal of molecular sciences · 2026Article
- NADPH oxidase 2 (NOX2)-independent inducers of neutrophil extracellular traps promote resolution of chronic inflammation.Redox biology · 2026Article
- Immune-mediated excitotoxicity in brain disorders.Nature reviews. Immunology · 2026Review
- Mechanistic insights into how cichoriin inhibits P2YBMC biotechnology · 2026Article
- Dapansutrile preserves pancreatic beta-cell function by regulating insulin vesicle membrane fusion and mitochondrial homeostasis.Diabetes, obesity & metabolism · 2026Article
- The NLRP3 Inflammasome: Mechanisms of Activation, Regulation, and Therapeutic Opportunities.MedComm · 2026Review
- Targeting pyroptosis in periodontitis: mechanisms and therapeutic strategies.Frontiers in immunology · 2026Review
- Biological Therapies for Urate Lowering and Inflammation Control in Gout Management.Journal of inflammation research · 2026Review
- From soluble uric acid to sodium urate crystal: immune metabolic inflammation driven by uric acid morphological transformation and mechanism-oriented therapy.Frontiers in immunology · 2026Review
- Radiation meets inflammation: NLRP3 inflammasome at the core of radiation-induced cardiac injury.Journal of translational medicine · 2025Review
- Sulphonylureas as Adjunct Therapeutic Agents in the Treatment of Autoimmune Conditions: A Narrative Review.Pharmacology research & perspectives · 2025Review
- NLRP3 inflammasome: structure, mechanism, drug-induced organ toxicity, therapeutic strategies, and future perspectives.RSC medicinal chemistry · 2025Review
- Role of Peripheral NLRP3 Inflammasome in Cognitive Impairments: Insights of Non-central Factors.Molecular neurobiology · 2025Review
- The Role of NLRP3 Inflammasome in Type 2 Diabetes Mellitus and Its Macrovascular Complications.Journal of clinical medicine · 2025Review
- Pyroptosis in Alzheimer's Disease: Mechanisms and Therapeutic Potential.Cellular and molecular neurobiology · 2025Review
- Updated insights into the molecular networks for NLRP3 inflammasome activation.Cellular & molecular immunology · 2025Review
- Targeting innate immune sensors for therapeutic strategies in infectious diseases.Journal of microbiology (Seoul, Korea) · 2025Review
39 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundActivation of the NLRP3 inflammasome in gout amplifies the inflammatory response and mediates further damage. In the current study, we assessed the therapeutic effect of OLT1177, an orally active NLRP3 inflammasome inhibitor that is safe in humans, in murine acute arthritis models.
methodsZymosan or monosodium urate (MSU) crystals were injected intra-articularly (i.a.) into mouse knee joints to induce reactive or gouty arthritis. Joint swelling, articular cell infiltration, and synovial cytokines were evaluated 25 hours and 4 hours following zymosan or MSU challenge, respectively. OLT1177 was administrated intraperitoneally by oral gavage or in the food by an OLT1177-enriched diet.
resultsOLT1177 reduced zymosan-induced joint swelling (p < 0.001), cell influx (p < 0.01), and synovial levels of interleukin (IL)-1β, IL-6, and chemokine (C-X-C motif) ligand 1 (CXCL1) (p < 0.05), respectively, when compared with vehicle-treated mice. Plasma OLT1177 levels correlated (p < 0.001) dose-dependently with reduction in joint inflammation. Treatment of mice with OLT1177 limited MSU crystal articular inflammation (p > 0.0001), which was associated with decreased synovial IL-1β, IL-6, myeloperoxidase, and CXCL1 levels (p < 0.01) compared with vehicle-treated mice. When administrated orally 1 hour after MSU challenge, OLT1177 reduced joint inflammation, processing of IL-1β, and synovial phosphorylated c-Jun N-terminal kinase compared with the vehicle group. Mice were fed an OLT1177-enriched diet for 3 weeks and then challenged i.a. with MSU crystals. Joint swelling, synovial IL-1β, and expression of Nlrp3 and Il1b were significantly reduced in synovial tissues in mice fed an OLT1177-enriched diet when compared with the standard diet group.
conclusionsOral OLT1177 is highly effective in ameliorating reactive as well as gouty arthritis.
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