Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, The Ohio State University, Columbus, OH, United States.
Antiviral Res. 2013 Aug;99(2):188-95. doi: 10.1016/j.antiviral.2013.05.013. Epub 2013 Jun 2.
Lactoferrin (LF) is a glycoprotein present in human milk with known antimicrobial effects. In vitro, LF has demonstrated antiviral activity against respiratory syncytial virus (RSV). We sought to assess the effect of bovine (b)LF in RSV replication, lung inflammation and function, cytokine profiles and clinical disease in an in vivo murine model.
Female BALB/c mice were inoculated with 10(7)PFU RSV A2 or 10% EMEM. bLF or placebo (DPBS) were administered once or twice daily by oral gavage or intraperitoneal (IP) injection at doses ranging from 2 to 10mg/animal/day, from 48h before until 96h post-RSV inoculation. Bronchoalveolar lavage (BAL), whole lung and serum samples were harvested on day 5 post-inoculation to asses RSV loads, lung inflammation and cytokine concentrations. Weight loss, airway obstruction and disease severity were assessed daily in all groups.
On day 5 post-inoculation BAL RSV loads, lung inflammation and serum innate, Th1, Th2 and Th17 cytokine concentrations showed no differences between RSV infected mice treated with bLF and RSV infected but untreated mice independent of bLF dosing and administration route (p>0.05). In addition, all bLF groups showed similar weight loss, degree of airway obstruction, and disease severity scores on days 1-5 post-inoculation which was comparable to infected untreated mice (p>0.05) but higher than uninfected controls.
Administration of oral or IP bLF at different doses did not demonstrate antiviral activity or significant effects on disease severity in the RSV mouse model. Whether these observations could be extrapolated to infants at risk for RSV infection needs to be further explored.
乳铁蛋白（LF）是一种存在于人乳中的糖蛋白，具有已知的抗菌作用。体外研究表明，LF 对呼吸道合胞病毒（RSV）具有抗病毒活性。我们试图评估牛（b）LF 对 RSV 复制、肺部炎症和功能、细胞因子谱以及体内鼠模型临床疾病的影响。
雌性 BALB/c 小鼠用 10（7）PFU RSV A2 或 10% EMEM 接种。bLF 或安慰剂（DPBS）通过口服灌胃或腹腔（IP）注射，每天一次或两次，在 RSV 接种前 48 小时至接种后 96 小时内，剂量范围为 2 至 10mg/动物/天。接种后第 5 天收获支气管肺泡灌洗液（BAL）、全肺和血清样本，以评估 RSV 载量、肺部炎症和细胞因子浓度。所有组均每日评估体重减轻、气道阻塞和疾病严重程度。
接种后第 5 天，BAL RSV 载量、肺部炎症和血清固有、Th1、Th2 和 Th17 细胞因子浓度在接受 bLF 治疗的 RSV 感染小鼠与未接受 bLF 治疗的 RSV 感染但未治疗的小鼠之间没有差异，与 bLF 剂量和给药途径无关（p>0.05）。此外，所有 bLF 组在接种后第 1-5 天的体重减轻、气道阻塞程度和疾病严重程度评分相似，与未感染未治疗的小鼠相当（p>0.05），但高于未感染对照小鼠。
在 RSV 小鼠模型中，不同剂量口服或 IP 给予 bLF 并未显示出抗病毒活性或对疾病严重程度的显著影响。这些观察结果是否可以外推到有 RSV 感染风险的婴儿，需要进一步探讨。
