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[柳氮磺胺吡啶及其代谢产物对免疫活性细胞的影响]

[Effect of salazosulfapyridine and its metabolites on immunocompetent cells].

作者信息

Ishibashi T, Hara A, Tsuboi I, Muraoka T, Shibata H, Tsunosue R, Shichijo S, Yokoyama M

出版信息

Ryumachi. 1989 Jun;29(3):178-84.

PMID:2573159
Abstract

Long-term administration of SASP does offer clinical benefit and has a demonstrable disease modifying effect in rheumatoid arthritis, though its mode of action remains obscure. We have studied the in vitro effects of SASP and its metabolites, that is SP, ASA, AcSP and AcASA, on the blast-formation of lymphocytes, the cytotoxic activity of NK cell, the phagocytosis and H2O2 production of monocyte and the fMLP-induced chemotaxis and superoxide anions production of PMNs. We have obtained the following results: (1) the blast-formation of lymphocytes by PHA and Protein A was significantly inhibited by SASP, but not by the metabolites; (2) the cytotoxic activity of the NK cell was inhibited by SP and AcSP, but not by SASP, ASA and AcASA; (3) on monocyte, SP, AcSP and AcASA inhibited phagocytosis, and all of drugs had no effect on the production of H2O2; (4) on PMNs, SASP, SP and ASA significantly inhibited fMLP-induced chemotaxis, and SASP and all of its metabolites significantly inhibited a release of superoxide anions by stimulation of fMLP and PMA; (5) SASP and ASA scavenged superoxide radical at the concentration comparable to clinical doses. In vivo, the above effects may be exhibited in proportion to each blood concentrations of drugs. In particular, it appears that SASP, SP and AcSP play an important role in the therapeutic efficacy in rheumatoid arthritis.

摘要

柳氮磺胺吡啶(SASP)的长期给药确实具有临床益处,并且在类风湿性关节炎中具有明显的疾病改善作用,尽管其作用方式仍不清楚。我们研究了SASP及其代谢产物,即磺胺吡啶(SP)、阿司匹林(ASA)、乙酰磺胺吡啶(AcSP)和乙酰水杨酸(AcASA)对淋巴细胞增殖、自然杀伤细胞(NK细胞)的细胞毒性活性、单核细胞的吞噬作用和过氧化氢生成以及甲酰甲硫氨酸-亮氨酸-苯丙氨酸(fMLP)诱导的中性粒细胞趋化性和超氧阴离子生成的体外影响。我们得到了以下结果:(1)SASP显著抑制了由植物血凝素(PHA)和蛋白A诱导的淋巴细胞增殖,但代谢产物没有这种作用;(2)SP和AcSP抑制NK细胞的细胞毒性活性,但SASP、ASA和AcASA没有这种作用;(3)对于单核细胞,SP、AcSP和AcASA抑制吞噬作用,并且所有药物对过氧化氢生成均无影响;(4)对于中性粒细胞,SASP、SP和ASA显著抑制fMLP诱导的趋化性,并且SASP及其所有代谢产物均显著抑制fMLP和佛波酯(PMA)刺激引起的超氧阴离子释放;(5)SASP和ASA在与临床剂量相当的浓度下清除超氧自由基。在体内,上述作用可能与每种药物的血药浓度成比例表现。特别是,似乎SASP、SP和AcSP在类风湿性关节炎的治疗效果中起重要作用。

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