In vitro and in vivo inhibitory effects of disodium cromoglycate on influenza virus infection

In vitro and in vivo inhibitory effects of disodium cromoglycate on influenza virus infection
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DOI:
10.1248/bpb.27.825
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发表时间:
2004-06-01
影响因子:
2
通讯作者:
Suzuki, Y
Suzuki, Y
中科院分区:
医学4区
文献类型:
--
作者:
Hidari, KIPJ;Tsujii, E;Suzuki, Y

文献摘要

被引文献

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甘草酸二钠(DSCG)是预防支气管哮喘和变应性鼻炎发作最安全的药物之一。DSCG对急性上呼吸道病毒感染的治疗效果尚存争议。我们在体内和体外研究了DSCG对流感病毒感染的抑制作用。采用小鼠呼吸道感染模型,评估了DSCG对病毒感染的体内作用。经鼻给药DSCG对流感病毒A/PR/8/34致小鼠死亡具有保护作用。我们通过(i)在病毒吸附前处理细胞,(ii)在病毒吸附时同时处理细胞,或(iii)在病毒吸附后处理细胞来分析DSCG的体外抗病毒作用。在病毒吸附期间或之后,而不是在病毒吸附之前,DSCG处理细胞可显著抑制流感病毒感染,表明DSCG对病毒感染后期事件起作用。DSCG在体外和体内均有抗流感作用,剂量与哮喘治疗相适应。DSCG对流感病毒神经氨酸酶和膜融合功能有微弱抑制作用,提示DSCG对病毒神经氨酸酶和融合活性的抑制可能部分介导了这种抗流感作用。我们的研究结果表明,包括儿童在内的DSCG患者的治疗可能有助于预防流感病毒感染。
Disodium cromoglycate (DSCG) is one of the safest drugs for the prevention of bronchial asthma and allergic rhinitis attacks. The effect of DSCG on acute upper respiratory tract viral infection is still controversial. Here we investigated DSCG inhibition of influenza virus infection in vivo and in vitro. In vivo effects of DSCG on viral infection were assessed using a murine model of respiratory tract infection. Intranasal administration of DSCG protected mice from death induced by infection with influenza virus A/PR/8/34. We analyzed DSCG anti-viral effects in vitro by either (i) treating cells prior to viral adsorption, (ii) treating cells concurrently with viral adsorption, or (iii) treating cells after viral adsorption. DSCG treatment of cells during or after, but not before, viral adsorption significantly inhibited influenza viral infection, indicating DSCG acts on events late in viral infection. DSCG exerts anti-influenza effect both in vitro and in vivo at the doses compatible with treatment for asthma. DSCG marginally inhibited influenza viral neuraminidase and membrane fusion functions, suggesting that DSCG inhibition of viral neuraminidase and fusion activities may partially mediate this anti-influenza effect. Our results indicate that treatment of patients including children with DSCG may take advantages for prevention from influenza virus infection.