Suppressive effects of the neutrophil elastase inhibitor sivelestat sodium hydrate on interleukin-1β production in lipopolysaccharide-stimulated porcine whole blood

中性粒细胞弹性蛋白酶抑制剂西维司他钠水合物对脂多糖刺激的猪全血中白细胞介素-1β产生的抑制作用

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Abstract

OBJECTIVE: Sivelestat sodium hydrate (Siv) is expected to be an effective therapy for acute respiratory distress syndrome, although its mechanism of action is not understood. In this study, we investigated which myeloid cells-derived cytokines were suppressed by Siv. METHODS: Continuous hemofiltration was performed by circulating fresh porcine blood through a semi-closed circuit. To ensure that leukocytes survived for 360 min, 5% glucose, heparin, and air were continuously injected. The control group received continuous administration of lipopolysaccharide (LPS) only, whereas the Siv group received LPS and Siv. Complete blood count, levels of various cytokines, and other variables were compared between the groups. RESULTS: Interleukin (IL)-1β level was significantly suppressed in the Siv group compared with that in the control group (p<0.05). CONCLUSIONS: The results suggested that Siv suppressed the production of IL-1β and possibly other cytokines by myeloid cells. Whether this suppression of cytokine production is caused directly by Siv or mediated via suppression of granulocyte elastase should be evaluated in the future.

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