Neutrophil elastase inhibitor (ONO-5046.Na) decreases production of proinflammatory cytokines by lipopolysaccharide-stimulated human monocytes.

Abstract

This study investigates in vitro effects of specific neutrophil elastase inhibitor ONO-5046.Na on production of proinflammatory cytokines by human monocytes in a neutrophil-free system. Isolated human monocytes were cultured with lipopolysaccharide in the presence or absence of ONO-5046.Na. The production of proinflammatory cytokines was assessed by the measurement of cytokine level in the culture supernatant. ONO-5046.Na significantly inhibited the production of IL-1 beta and IL-6 at the doses between 10(-9) and 10(-7) M, and TNF-alpha at the doses between 10(-9) and 10(-4) M. These results suggest that ONO-5046.Na at clinically available concentrations can inhibit the cytokine production by monocytes. This drug could act as a dual inhibitor of neutrophils and monocytes in inflammatory tissue destruction.