Neutrophil elastase inhibitor (ONO-5046.Na) decreases production of proinflammatory cytokines by lipopolysaccharide-stimulated human monocytes.
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.
Haga
Y
Y
Department of Surgery II, Kumamoto University Medical School, Japan.
Ogawa
M
M
D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D008070:Lipopolysaccharides; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; C069195:sivelestat; D019272:Leukocyte Elastase; D005998:Glycine