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

Abstract

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. Continuous hemofiltration was performed by circulating fresh porcine blood through a semi-closed circuit. To ensure that leukocytes survived for 360min, 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. Interleukin (IL)-1β level was significantly suppressed in the Siv group compared with that in the control group (p<0.05). 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.