ArticleAntimicrobial agents and chemotherapy2016
Clofazimine Biocrystal Accumulation in Macrophages Upregulates Interleukin 1 Receptor Antagonist Production To Induce a Systemic Anti-Inflammatory State.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 38 citations in OpenAlex.
- Evaluation of clofazimine-bedaquiline combination as a candidate regimen for macrolide-resistantAntimicrobial agents and chemotherapy · 2026Article
- Targeted delivery of antitubercular drugs using glucan lipid particles.Microbiology spectrum · 2025Article
- Molecular pathogenesis of Cryptosporidium and advancements in therapeutic interventions.Parasite (Paris, France) · 2025Review
- Quantitative Raman chemical imaging of intracellular drug-membrane aggregates and small molecule drug precipitates in cytoplasmic organelles.Advanced drug delivery reviews · 2023Review
- Distinguishing the Concentration- vs. Bioaccumulation-Dependent Immunological and Metabolic Effects of Clofazimine.Pharmaceutics · 2023Article
- Proteomic analysis and identification reveal the anti-inflammatory mechanism of clofazimine on lipopolysaccharide-induced acute lung injury in mice.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Article
- Respirable Clofazimine Particles Produced by Air Jet Milling Technique Are Efficacious in Treatment of BALB/c Mice with Chronic Mycobacterium tuberculosis Infection.Antimicrobial agents and chemotherapy · 2022Article
- Molecular design of a pathogen activated, self-assembling mechanopharmaceutical device.Journal of controlled release : official journal of the Controlled Release Society · 2022Review
- Adapting Clofazimine for Treatment of Cutaneous Tuberculosis by Using Self-Double-Emulsifying Drug Delivery Systems.Antibiotics (Basel, Switzerland) · 2022Review
- An Adaptive Biosystems Engineering Approach towards Modeling the Soluble-to-Insoluble Phase Transition of Clofazimine.Pharmaceutics · 2021Article
- The Effect of Tuberculosis Antimicrobials on the Immunometabolic Profiles of Primary Human Macrophages Stimulated withInternational journal of molecular sciences · 2021Article
- Activity of Clofazimine and TBI-166 against Mycobacterium tuberculosis in Different Administration Intervals in Mouse Tuberculosis Models.Antimicrobial agents and chemotherapy · 2021Article
- Drug Delivery Systems on Leprosy Therapy: Moving Towards Eradication?Pharmaceutics · 2020Review
- Clofazimine is a broad-spectrum coronavirus inhibitor that antagonizes SARS-CoV-2 replication in primary human cell culture and hamsters.Research square · 2020Article
- Clofazimine Reduces the Survival ofACS infectious diseases · 2020Article
- Understanding and Exploiting the Effect of Tuberculosis Antimicrobials on Host Mitochondrial Function and Bioenergetics.Frontiers in cellular and infection microbiology · 2020Review
- Photoacoustic imaging of clofazimine hydrochloride nanoparticle accumulation in cancerous vs normal prostates.PloS one · 2019Article
- Synthesis and Characterization of a Biomimetic Formulation of Clofazimine Hydrochloride Microcrystals for Parenteral Administration.Pharmaceutics · 2018Article
- An Expandable Mechanopharmaceutical Device (1): Measuring the Cargo Capacity of Macrophages in a Living Organism.Pharmaceutical research · 2018Article
- An Expandable Mechanopharmaceutical Device (2): Drug Induced Granulomas Maximize the Cargo Sequestering Capacity of Macrophages in the Liver.Pharmaceutical research · 2018Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Clofazimine (CFZ) is a poorly soluble antibiotic and anti-inflammatory drug indicated for the treatment of leprosy. In spite of its therapeutic value, CFZ therapy is accompanied by the formation of drug biocrystals that accumulate within resident tissue macrophages, without obvious toxicological manifestations. Therefore, to specifically elucidate the off-target consequences of drug bioaccumulation in macrophages, we compared the level of inflammasome activation in CFZ-accumulating organs (spleen, liver and lung) in mice after 2 and 8 weeks of CFZ treatment when the drug exists in soluble and insoluble (biocrystalline) forms, respectively. Surprisingly, the results showed a drastic reduction in caspase 1 and interleukin-1β (IL-1β) cleavage in the livers of mice treated with CFZ for 8 weeks (8-week-CFZ-treated mice) compared to 2-week-CFZ-treated and control mice, which was accompanied by a 3-fold increase in hepatic IL-1 receptor antagonist (IL-1RA) production and a 21-fold increase in serum IL-1RA levels. In the lung and spleen, IL-1β cleavage and tumor necrosis factor alpha expression were unaffected by soluble or biocrystal CFZ forms. Functionally, there was a drastic reduction of carrageenan- and lipopolysaccharide-induced inflammation in the footpads and lungs, respectively, of 8-week-CFZ-treated mice. This immunomodulatory activity of CFZ biocrystal accumulation was attributable to the upregulation of IL-1RA, since CFZ accumulation had minimal effect in IL-1RA knockout mice or 2-week-CFZ-treated mice. In conclusion, CFZ accumulation and biocrystal formation in resident tissue macrophages profoundly altered the host's immune system and prompted an IL-1RA-dependent, systemic anti-inflammatory response.
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