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Original Article
- Infection
- The Effects of Flecainide Acetate on Inflammatory-Immune Response in Lipopolysaccharide-Stimulated Neutrophils and on Mortality in Septic Rats
- Shi Young Chung, Jinyoung Kim, Hong Bum Bae, Tran Duc Tin, Wan Ju, Sang Hyun Kwak
- Acute Crit Care. 2018;33(1):34-41. Published online February 28, 2018
- DOI: https://doi.org/10.4266/acc.2017.00577
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Abstract
PDF - Background
Flecainide acetate is a drug used primarily for cardiac arrhythmia. Some studies also imply that flecainide acetate has the potential to regulate inflammatory-immune responses; however, its mechanism of action is contended. We determined the effects of flecainide acetate on lipopolysaccharide (LPS)-stimulated human neutrophils in vitro and on mortality in a septic rat model.
Methods
Neutrophils from human blood were cultured with varying concentrations of flecainide acetate (1 μM, 10 μM, or 100 μM) with or without LPS (100 ng/ml). To assess neutrophil activation, the protein levels of tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 and IL-8 were measured after a 4-hour culture period. To assess the intracellular signaling pathways, the levels of phosphorylation of p38 mitogen-activated protein kinase (p38), extracellular signal-regulated kinase (ERK) 1/2, and c-Jun N-terminal kinase (JNK) were measured after a 30-minute culture period, and the nuclear translocation of nuclear factor (NF)-κB was measured after a 1-hour culture period. Additionally, the survival rate was investigated in a rat sepsis model.
Results
Flecainide acetate down-regulated the activation of proinflammatory cytokines, including TNF-α and IL-6 and IL-8, and intracellular signaling pathways including ERK 1/2 and NF-κB. Flecainide acetate also improved the survival rate in the rat sepsis model.
Conclusions
Collectively, these findings indicate that flecainide acetate can improve survival in a rat sepsis model by attenuating LPS-induced neutrophil responses. We therefore suggest that flecainide acetate plays an important role in modulating inflammatoryimmune responses.
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