Effect of amiodarone on release of cytokines from mouse alveolar macrophages pretreated with eicosapentaenoic acid.
I studied the effect of amiodarone, a cationic amphiphilic drug, on the cytokine release and protein kinase C (PKC) activity of mouse alveolar macrophages. In addition, I examined the relationship between amiodarone and eicosapentaenoic acid (EPA) with respect to the cytokine release. The decrease in cell number caused by amiodarone was depressed by pretreatment of the macrophages with EPA for 2 days and co-treatment for 1 day. These changes reflected the potency of EPA to protect against the cell injury elicited by amiodarone. As regards to the cytokine release, amiodarone caused an increase in interleukin (IL)-1 alpha, IL-1 beta and tumor necrosis factor (TNF) alpha release from macrophages. As EPA suppressed this increase in cytokine levels, I considered that the protective effect of EPA may be extended to the acute release of cytokines. PKC activity was increased by amiodarone, and this increase was depressed by EPA. These changes were well-related to the results on cytokine levels in this study, indicating that amiodarone firstly activated PKC, leading to the stimulation of release of cytokines and that pretreatment with EPA prevented these effects. I conclude that mouse alveolar macrophages treated with amiodarone show activated release of cytokines and that EPA depresses these increases, thereby demonstrating EPA's anti-inflammatory effect and protective action against injury of alveolar macrophages.
Futamura
Y
Y
Department of Pharmacology, Toho University School of Medicine, Tokyo, Japan.
D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D002452:Cell Count / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D016676:Macrophages, Alveolar / Q000187:drug effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011493:Protein Kinase C / Q000378:metabolism
D016207:Cytokines; D015118:Eicosapentaenoic Acid; D011493:Protein Kinase C; D000638:Amiodarone