Gorskaya Yu F, Grabko V I, Konopleva M V, Suslov A P, Nesterenko V G
Laboratory of Immunity Regulation, Laboratory of Bioactive Nanostructures, and Laboratory of Immunity Mediators and Effectors, N. F. Gamaleya Research Institute of Epidemiology and Microbiology, the Ministry of Health of the Russian Federation, Moscow, Russia,
Bull Exp Biol Med. 2015 Jun;159(2):240-4. doi: 10.1007/s10517-015-2932-7. Epub 2015 Jun 20.
The efficiency of cloning of bone marrow multipotent stromal cells (ECF-MSC) from CBA mice and the MSC counts in the femoral bone increased 24 h after a single in vivo (but not in vitro) injection of kagocel (active substance of antiviral drug Kagocel (®) ) 1.4 times (in response to 50-80 μg) and 4.6 times (in response to 250 μg). The maximum increase of ECF-MSC in response to 50 μg per mouse was detected just 1 h after Kagocel injection to intact mice and to mice previously receiving the drug for 3 days (2 and 1.7 times, respectively). The increase of ECF-MSC was 3-fold less intense in response to oral Kagocel in a dose of 250 μg/mouse vs. intraperitoneal Kagocel, ECF-MSC corresponding to its level in response to oral Poly (I:C). In vivo Kagocel led to emergence of proinflammatory cytokine IFN-γ, IL-1β, and IL-8 mRNA in primary cultures of bone marrow stromal cells. Serum concentrations of IL-2, IL-5, IL-10, GM-CSF, IFN-γ, TNF-α, IL-4, and IL-12 increased 1.5 and 2 times just 1 h after Kagocel injection in doses of 30-50 and 250 μg, respectively, to intact mice and to animals previously treated with the drug for 3 days. The cytokine concentrations normalized after 3 h and increased again after 24 h, though did not reach the levels recorded 1 h after the drug injection. These data indicated that the therapeutic and preventive effects of Kagocel, together with its previously demonstrated stimulation of α- and β-interferon production during several days, could be due to the capacity of this drug to increase the bone marrow ECF-MSC, serum cytokine concentrations, and induce the expression of proinflammatory cytokine genes in the bone marrow stromal cells 1 h after its injection.
对CBA小鼠的骨髓多能基质细胞（ECF-MSC）进行克隆的效率以及股骨中的MSC数量，在单次体内（而非体外）注射卡古缩宫素（抗病毒药物Kagocel（®）的活性物质）24小时后增加，注射50 - 80μg时增加1.4倍，注射250μg时增加4.6倍。对完整小鼠和先前连续3天接受该药物的小鼠注射50μg卡古缩宫素后，仅在1小时就检测到ECF-MSC的最大增加量（分别为2倍和1.7倍）。与腹腔注射卡古缩宫素相比，口服250μg/小鼠剂量的卡古缩宫素时，ECF-MSC的增加强度低3倍，口服卡古缩宫素时ECF-MSC的水平与口服聚肌胞苷酸（Poly（I:C））时相当。体内注射卡古缩宫素导致骨髓基质细胞原代培养物中促炎细胞因子IFN-γ、IL-1β和IL-8的mRNA出现。对完整小鼠和先前用该药物处理3天的动物分别注射30 - 50μg和250μg卡古缩宫素后，仅在1小时血清中IL-2、IL-5、IL-10、GM-CSF、IFN-γ、TNF-α、IL-4和IL-12的浓度就分别增加1.5倍和2倍。细胞因子浓度在3小时后恢复正常，24小时后再次升高，但未达到药物注射后1小时记录的水平。这些数据表明，卡古缩宫素的治疗和预防作用，连同其先前证明的在数天内刺激α和β干扰素产生的作用，可能归因于该药物在注射后1小时增加骨髓ECF-MSC、血清细胞因子浓度以及诱导骨髓基质细胞中促炎细胞因子基因表达的能力。
