Tazulakhova E B, Parshina O V, Guseva T S, Ershov F I
N.F. Gamaleya Institute of Microbiology and Epidemiology, RAMS, Moscow, Russia.
J Interferon Cytokine Res. 2001 Feb;21(2):65-73. doi: 10.1089/107999001750069926.
This review describes a long-standing experience of screening for interferon (IFN) inducers in Russia. IFN inducers represent a special group of potential antiviral compounds. The main requirements for them are (1) high IFN-inducing activity, (2) absence of side effects, (3) wide spectrum of antimicrobial activity, (4) broad therapeutic security and, (5) good solubility in water and biologic liquids. IFN inducers stimulate IFN production in different cells and organs, and that determines the strategy for their application. Amixin (OOO "Lancepharm," Moscow, Russia) induces IFN-alpha/beta production mostly in T cells. Cycloferon (NTFF "Polysan," St. Petersburg, Russia) stimulates B cells and macrophages to produce almost pure IFN-alpha. Double-stranded RNA (dsRNA) and polyphenols of natural origin stimulate IFN production in different populations of immunocytes. Only polymers, such as Larifan (Riga, Latvia), Kagocel ("NIARnedicplus," Moscow, Russia), and Ragosin (N.F. Gamaleya Institute, Moscow, Russia), induce IFN synthesis in muscles, so they may be effective against rabies. Cycloferon, Larifan, and Kagocel, which induce IFN formation in lungs, may be effective against influenza and rhinoviral infections. Cycloferon and Larifan stimulate IFN production in liver and spleen and may be effective against hepatitis B. Oral compounds (Amixin, Kagocel) that stimulate IFN production in intestines may be effective against hepatitis A and enteroviral infections. Low molecular weight inducers (Amixin, Cycloferon, Kagocel) that penetrate the blood-brain barrier may be active against viral encephalitis. At present, clinical trials of IFN inducers are limited, but in the near future, IFN inducers may be used against very different infections and conditions.
本综述介绍了俄罗斯在干扰素(IFN)诱导剂筛查方面的长期经验。IFN诱导剂是一类特殊的潜在抗病毒化合物。对它们的主要要求包括:(1)高IFN诱导活性;(2)无副作用;(3)广谱抗菌活性;(4)广泛的治疗安全性;(5)在水和生物液体中良好的溶解性。IFN诱导剂可刺激不同细胞和器官产生IFN,这决定了其应用策略。阿咪新(俄罗斯莫斯科OOO“Lancepharm”公司)主要在T细胞中诱导IFN-α/β产生。环磷酰胺(俄罗斯圣彼得堡NTFF“Polysan”公司)刺激B细胞和巨噬细胞产生几乎纯的IFN-α。天然来源的双链RNA(dsRNA)和多酚可刺激不同免疫细胞群体产生IFN。只有聚合物,如拉里凡(拉脱维亚里加)、卡古西尔(俄罗斯莫斯科“NIARnedicplus”公司)和拉戈辛(俄罗斯莫斯科N.F.加马列亚研究所),能在肌肉中诱导IFN合成,因此它们可能对狂犬病有效。能在肺部诱导IFN形成的环磷酰胺、拉里凡和卡古西尔可能对流感和鼻病毒感染有效。环磷酰胺和拉里凡可刺激肝脏和脾脏产生IFN,可能对乙型肝炎有效。能在肠道刺激IFN产生的口服化合物(阿咪新、卡古西尔)可能对甲型肝炎和肠道病毒感染有效。能穿透血脑屏障的低分子量诱导剂(阿咪新、环磷酰胺、卡古西尔)可能对病毒性脑炎有活性。目前,IFN诱导剂的临床试验有限,但在不久的将来,IFN诱导剂可能用于治疗多种不同的感染和病症。