Effects of suplatast tosilate (IPD Capsules) on the production of active oxygen by neutrophils and of IL-8 by mononuclear cells.
In bronchial asthma, eosinophils and neutrophils are activated, so that the production of active oxygen species increases, causing airway epithelial injury. Suplatast tosilate (IPD Capsules) is a novel immunomodulating antiallergic drug that acts against bronchial asthma through a new mechanism. To evaluate the effects of suplatast tosilate on mononuclear cell-mediated IL-8 production, and neutrophil-mediated active oxygen species production at sites of inflammation, we collected peripheral blood from healthy subjects and separated the neutrophils as well as mononuclear cells. Suplatast tosilate was added at a concentration of 1 x 10(-6), 1 x 10(-7) or 1 x 10(-8) M, and cells were incubated for 10 min at 37 degrees C. Then, the neutrophils were stimulated with fMLP, and luminol-dependent chemiluminescence (LDCL) was measured, while IL-8 production was determined with an ELISA kit. Suplatast tosilate (1 x 10(-6) M) inhibited neutrophil-mediated active oxygen species production by 12.4% in terms of the peak, and by 16% in terms of the integral value. Moreover, it significantly inhibited mononuclear cell-mediated IL-8 production at concentrations of 1 x 10(-6), 1 x 10(-7) and 1 x 10(-8) M, in a concentration-dependent manner. This study indicated that suplatast tosilate may inhibit neutrophil infiltration by suppressing monocyte-mediated IL-8 production, and it may also inhibit the activation of neutrophils at sites of inflammation. These results suggest the possibility that suplatast tosilate may not only be of benefit for asthma, but may also prevent or control pulmonary fibrosis or emphysema, for which no effective treatment is presently available.
Tohda
Y
Y
Fourth Department of Internal Medicine, Kinki University School of Medicine 377-2, Ohno-Higashi, Osaka-Sayama, Osaka, 589-0014 Japan. access-planning@eva.hi-ho.ne.jp
Kubo
H
H
Haraguchi
R
R
Iwanaga
T
T
Fukuoka
M
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D001190:Arylsulfonates / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000096:biosynthesis*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013452:Sulfonium Compounds / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D018926:Anti-Allergic Agents; D001190:Arylsulfonates; D016209:Interleukin-8; D017382:Reactive Oxygen Species; D013452:Sulfonium Compounds; C073028:suplatast tosilate