Ｓａｌａｚｏｓｕｌｐｈａｐｙｒｉｄｉｎｅ，Ｐｒｅｄｏｎｉｚｏｌｏｎｅの好中球機能に及ぼす影響とＳｏｄｉｕｍ ｆｅｒｒｏｕｓ ｃｉｔｒａｔｅとの併用効果についての検討

Abstract

INTRODUCTION: We previously investigated the effects of sodium ferrous citrate (SFC) on neutrophils in vitro, and revealed that SFC inhibited neutrophil functions such as superoxide production and chemotaxis. Salazosulphapyridine (SASP) and predonizolone (PSL) are widely used for treatment of ulcerative colitis (UC). In this study, we evaluated the actions of SASP or PSL on the functions of neutrophils. Moreover, we evaluated the combined effects of SASP or PSL and SFC on neutrophil functions.METHODS: Neutrophils were incubated with SASP or PSL in the absence or presence of SFC. For determination of superoxide production, neutrophils were further stimulated with phorbol myristate acetate (PMA), complement-opsonized zymosan (OPZ) or N-formyl-menthionyl-leucyl-phenylalamine (fMLP). The superoxide production was measured on the basis of superoxide dismutase-inhibitable cytochrome c. Neutrophil migration was measured by a Boyden chamber assay using zymosan-activated serum (C5a) as a chemotactic factor. To examine the expression of CD11b and CD62L, neutrophils were stimulated with fMLP, and then incubated with phycoerythrin-labeled anti-CD11b and FITC-labeled anti-CD62L monoclonal antibodies, and the expression of CD11b and CD62L were analyzed by flow cytometry.RESULTS: SASP dose-dependently inhibited the superoxide production induced by all stimuli examined, whereas, PSL did not affect the superoxide production. SASP and PSL inhibited chemotaxis toward C5a in a dose-dependent fashion. Furthermore, SASP and PSL inhibited the fMLP-induced up-regulation of CD11b and down-regulation of CD62L. Interestingly, the combinats on the SASP or PSL and SFC exerted the strong inhibitory actions on the superoxide production and neutrophil migration compared with SASP and PSL alone.CONCLUSIONS: The present observations suggest that the combined administration of SASP or PSL with SFC may have a potential to reduce mucosal injury by suppressing neutrophil functions in UC.