Effects of suplatast tosilate (IPD Capsules((R))) 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 i njury. Suplatast tosilate (IPD Capsules (R)) is a novel immunomodulating an tiallergic 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 a t sites of inflammation, we collected peripheral blood from healthy subject s and separated the neutrophils as well as mononuclear cells. Suplatast tos ilate 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 degreesC. Then, the neutrophil s 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 oxyg en species production by 12.4% in terms of the peak, and by 16% in terms of the integral value. Moreover, ii. 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 mono cyte-mediated IL-8 production, and it may also inhibit the activation of ne utrophils at sites of inflammation. These results suggest the possibility t hat 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. (C) 2001 Elsevier Science B.V. All rights reserved.