Viland H, Blomgren H
Department of General Oncology, Karolinska Hospital, Stockholm, Sweden.
Int J Immunopharmacol. 1988;10(7):879-87. doi: 10.1016/0192-0561(88)90013-6.
The immunomodulatory agent RU 41740 (Biostim), which is derived from Klebsiella pneumoniae, may augment mitogenic responses of purified human blood lymphocytes. In non-purified preparations, however, responses may be sharply reduced due to the fact that Biostim induces monocytes to secrete immunosuppressive factors. This investigation has shown that both these biological activities can be exerted by a single, major glucoprotein fraction of Biostim termed F1. The Biostim-induced suppression of mitogen responses was not blocked by antibodies directed against IFN alpha or IFN gamma, thus speaking against IFN as being a mediator of suppression. Reduced suppression, however, was observed in the presence of drugs which inhibit arachidonic acid transformation. The cyclo-oxygenase inhibitors meclofenamic acid and indomethacin, which diminish biosynthesis of prostaglandins, could partially block the Biostim-induced suppression. Such an effect was not observed with 5,8,11-eicosatrynoic acid (ETI) which is an inhibitor of 12-lipoxygenase and leukotriene biosynthesis. Combinations of ETI and meclofenamic acid, however, were more potent than the latter tested separately. Another drug termed diclofenac Na, which apart from being an inhibitor of cyclo-oxygenase, rapidly clears cells of free arachidonic acid by binding to triglycerides, was found to be the most potent in preventing Biostim-induced suppression of mitogen responses. It is concluded that Biostim-exposed monocytes liberate increased amounts of immunosuppressive eicosanoids such as prostaglandins.
免疫调节剂RU 41740（生物刺激素）源自肺炎克雷伯菌，可能增强纯化的人血淋巴细胞的促有丝分裂反应。然而，在非纯化制剂中，由于生物刺激素诱导单核细胞分泌免疫抑制因子，反应可能会急剧降低。本研究表明，生物刺激素的这两种生物学活性均可由其单一的主要糖蛋白组分F1发挥。生物刺激素诱导的促有丝分裂反应抑制未被针对IFNα或IFNγ的抗体阻断，因此排除了IFN作为抑制介质的可能性。然而，在存在抑制花生四烯酸转化的药物时，观察到抑制作用减弱。环氧化酶抑制剂甲氯芬那酸和吲哚美辛可减少前列腺素的生物合成，可部分阻断生物刺激素诱导的抑制作用。作为12-脂氧合酶和白三烯生物合成抑制剂的5,8,11-二十碳三烯酸（ETI）未观察到这种效果。然而，ETI与甲氯芬那酸的组合比单独测试的后者更有效。另一种药物双氯芬酸钠，除了是环氧化酶抑制剂外，还通过与甘油三酯结合迅速清除细胞中的游离花生四烯酸，被发现是预防生物刺激素诱导的促有丝分裂反应抑制作用最有效的药物。得出的结论是，暴露于生物刺激素的单核细胞会释放出更多的免疫抑制类花生酸，如前列腺素。
