Sato Masatoki, Hashimoto Koichi, Kawasaki Yukihiko, Hosoya Mitsuaki
Department of Paediatrics, Fukushima Medical University, Fukushima, Japan.
Antivir Ther. 2018;23(5):435-441. doi: 10.3851/IMP3222.
Immune response after intravenous peramivir administration, which is approved for children with influenza infection in Japan, is unclear.
Kinetics of viral load and serum cytokine levels before and after peramivir therapy were analysed in 17 and 8 hospitalized children infected with influenza A and B, respectively. Additionally, haemagglutination inhibition (HI) titre was measured. The first day of hospital admission was defined as day 0.
Serum interleukin (IL)-6 levels in influenza-A-infected children significantly decreased after peramivir administration, unlike in those with influenza B where a decrease on day 1 was followed by an increase on day 2. Serum IL-6 kinetics were similar to viral load kinetics in both influenza-A- and B-infected children between days 0 and 2. Serum IL-8 levels gradually decreased after peramivir therapy in influenza-A-infected children but increased between days 1 and 2 in influenza-B-infected children. Conversely, serum IL-10 levels gradually decreased over time. Serum interferon-γ and granulocyte macrophage colony-stimulating factor levels remained low until day 5. Day 0-4 serum HI titres were <4-fold in all children infected with influenza A or B. Additionally, day 5 HI titres were positive in 4 of 6 influenza A cases and all 3 influenza B cases.
Our results suggest that viral load and inflammatory cytokine kinetics were associated with the antiviral therapy used and that second peramivir administration should be considered in influenza B. The results also highlight antiviral agents as key determinants of the clinical course of influenza virus infection in children.
在日本已获批用于流感感染儿童的静脉注射帕拉米韦后的免疫反应尚不清楚。
分别对17例甲型流感和8例乙型流感住院患儿在帕拉米韦治疗前后的病毒载量动力学和血清细胞因子水平进行分析。此外，还测量了血凝抑制（HI）滴度。入院第一天定义为第0天。
甲型流感感染患儿在给予帕拉米韦后血清白细胞介素（IL）-6水平显著下降，而乙型流感感染患儿在第1天下降后第2天又升高。在第0天至第2天期间，甲型和乙型流感感染患儿的血清IL-6动力学与病毒载量动力学相似。甲型流感感染患儿在接受帕拉米韦治疗后血清IL-8水平逐渐下降，而乙型流感感染患儿在第1天至第2天期间升高。相反，血清IL-10水平随时间逐渐下降。血清干扰素-γ和粒细胞巨噬细胞集落刺激因子水平在第5天前一直较低。所有甲型或乙型流感感染患儿在第0天至第4天的血清HI滴度均<4倍。此外，6例甲型流感病例中有4例在第5天HI滴度呈阳性，3例乙型流感病例全部呈阳性。
我们的结果表明，病毒载量和炎性细胞因子动力学与所使用的抗病毒治疗相关，对于乙型流感应考虑再次给予帕拉米韦。这些结果还突出了抗病毒药物是儿童流感病毒感染临床病程的关键决定因素。
