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The Potential of Fluocinolone Acetonide to Mitigate Inflammation and Lipid Accumulation in 2D and 3D Foam Cell Cultures.

ABSTRACT: Inflammation plays an important role in all stages of atherosclerosis development. Therefore, the use of anti-inflammatory drugs could reduce the risk of major adverse cardiovascular events due to atherosclerosis. Herein, we explored the capacity of fluocinolone acetonide (FA), a glucocorticoid (GC), in modulating foam cell formation and response. Human THP-1 derived foam cells were produced using 100??g/mL oxidized low-density lipoproteins (OxLDL) and fetal bovine serum (1 and 10%). 2D cultures of these cells were treated with FA (0.1, 1, 10, and 50??g/mL) in comparison with dexamethasone (Dex). Results showed that treatment with 0.1 and 1??g/mL FA and Dex improved foam cell survival. FA and Dex also inhibited inflammatory cytokine (CD14, M-CSF, MIP-3?, and TNF-?) secretion. Notably, at the concentration of 1??g/mL, both FA and Dex reduced cholesteryl ester accumulation. Compared to Dex, FA was significantly better in reducing lipid accumulation at the therapeutic concentrations of 1 and 10??g/mL. In a novel 3D foam cell spheroid model, FA was shown to be more effective than Dex in diminishing lipid accumulation, at the concentration of 0.1??g/mL. Taken together, FA was demonstrated to be effective in preventing both lipid accumulation and inflammation in foam cells.

SUBMITTER: Nguyen LTH

PROVIDER: S-EPMC6282138 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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The Potential of Fluocinolone Acetonide to Mitigate Inflammation and Lipid Accumulation in 2D and 3D Foam Cell Cultures.

Nguyen Luong T H LTH Muktabar Aristo A Tang Jinkai J Wong Yee Shan YS Thaxton Colby S CS Venkatraman Subbu S SS Ng Kee Woei KW

BioMed research international 20181122

Inflammation plays an important role in all stages of atherosclerosis development. Therefore, the use of anti-inflammatory drugs could reduce the risk of major adverse cardiovascular events due to atherosclerosis. Herein, we explored the capacity of fluocinolone acetonide (FA), a glucocorticoid (GC), in modulating foam cell formation and response. Human THP-1 derived foam cells were produced using 100 <i>μ</i>g/mL oxidized low-density lipoproteins (OxLDL) and fetal bovine serum (1 and 10%). 2D c ...[more]

PMID: 30596089

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Project description:To evaluate the 3-year incremental cost-effectiveness of fluocinolone acetonide implant versus systemic therapy for the treatment of noninfectious intermediate, posterior, and panuveitis.Randomized, controlled, clinical trial.Patients with active or recently active intermediate, posterior, or panuveitis enrolled in the Multicenter Uveitis Steroid Treatment Trial.Data on cost and health utility during 3 years after randomization were evaluated at 6-month intervals. Analyses were stratified by disease laterality at randomization (31 unilateral vs 224 bilateral) because of the large upfront cost of the implant.The primary outcome was the incremental cost-effectiveness ratio (ICER) over 3 years: the ratio of the difference in cost (in United States dollars) to the difference in quality-adjusted life-years (QALYs). Costs of medications, surgeries, hospitalizations, and regular procedures (e.g., laboratory monitoring for systemic therapy) were included. We computed QALYs as a weighted average of EQ-5D scores over 3 years of follow-up.The ICER at 3 years was $297,800/QALY for bilateral disease, driven by the high cost of implant therapy (difference implant - systemic [?]: $16,900; P < 0.001) and the modest gains in QALYs (? = 0.057; P = 0.22). The probability of the ICER being cost-effective at thresholds of $50,000/QALY and $100,000/QALY was 0.003 and 0.04, respectively. The ICER for unilateral disease was more favorable, namely, $41,200/QALY at 3 years, because of a smaller difference in cost between the 2 therapies (? = $5300; P = 0.44) and a larger benefit in QALYs with the implant (? = 0.130; P = 0.12). The probability of the ICER being cost-effective at thresholds of $50,000/QALY and $100,000/QALY was 0.53 and 0.74, respectively.Fluocinolone acetonide implant therapy was reasonably cost-effective compared with systemic therapy for individuals with unilateral intermediate, posterior, or panuveitis but not for those with bilateral disease. These results do not apply to the use of implant therapy when systemic therapy has failed or is contraindicated. Should the duration of implant effect prove to be substantially >3 years or should large changes in therapy pricing occur, the cost-effectiveness of implant versus systemic therapy would need to be reevaluated.

Dataset Information

The Potential of Fluocinolone Acetonide to Mitigate Inflammation and Lipid Accumulation in 2D and 3D Foam Cell Cultures.

Publications

The Potential of Fluocinolone Acetonide to Mitigate Inflammation and Lipid Accumulation in 2D and 3D Foam Cell Cultures.

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