Philot Pavão Beatriz, Demarque Kelly Cristina, Meuser Batista Marcos, Melo de Oliveira Gabriel, França da Silva Cristiane, Guedes da Silva Francisca Hildemagna, Gonçalves Caputo Luzia Fátima, Machado Cascabulho Cynthia, Barcinski Marcello André, Correia Soeiro Maria de Nazaré
1Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Av. Brasil, 4365, Manguinhos, Rio de Janeiro, RJ Brazil.
2Laboratório de Patologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Av. Brasil, 4365, Manguinhos, Rio de Janeiro, RJ Brazil.
J Venom Anim Toxins Incl Trop Dis. 2018 Aug 30;24:25. doi: 10.1186/s40409-018-0157-8. eCollection 2018.
Autologous whole blood (AWB) administration is described as alternative/complementary medical practice widely employed in medical and veterinary therapy against infections, chronic pathologies and neoplasias. Our aim is to investigate biological effect of AWB using healthy murine models under the course of acute infection.
The first set of studies consisted of injecting different volumes of AWB and saline (SAL) into the posterior region of quadriceps muscle of healthy male Swiss mice under distinct therapeutic schemes evaluating: animal behavior, body and organ weight, hemogram, plasmatic biochemical markers for tissue damage and inflammatory cytokine levels and profile. To assess the impact on the experimental infection, different schemes (prior and post infection) and periods of AWB administration (from one up to 10 days) were conducted, also employing heterologous whole blood (HWB) and evaluating plasma cytokine profile.
No major adverse events were observed in healthy AWB-treated mice, except gait impairment in animals that received three doses of 20 μL AWB in the same hind limb. AWB and SAL triggered an immediate polymorphonuclear response followed by mononuclear infiltrate. Although SAL triggered an inflammatory response, the kinetics and intensity of the histological profile and humoral mediator levels were different from AWB, the latter occurring earlier and more intensely with concomitant elevation of plasma IL-6. Inflammatory peak response of SAL, mainly composed of mononuclear cells with IL-10, was increased at 24 h. According to the mouse model of acute infection, only minor decreases (< 30%) in the parasitemia levels were produced by AWB and HWB given before and after infection, without protecting against mortality. Rises in IFN-gamma, TNF-alpha and IL-6 were detected at 9 dpi in all infected animals as compared to uninfected mice but only Bz displayed a statistically significant diminution ( 0.02) in TNF-alpha levels than infected and untreated mice.
This study revealed that the use of autologous whole blood (AWB) in the acute model employed was unable to reduce the parasitic load of infected mice, providing only a minor decrease in parasitemia levels (up to 30%) but without protecting against animal mortality. Further studies will be necessary to elucidate the effective impact of this procedure.
自体全血（AWB）输注被描述为一种替代/补充医学疗法，广泛应用于医学和兽医领域，用于对抗感染、慢性疾病和肿瘤。我们的目的是在急性感染过程中，使用健康的小鼠模型研究AWB的生物学效应。
第一组研究包括在不同的治疗方案下，将不同体积的AWB和生理盐水（SAL）注射到健康雄性瑞士小鼠股四头肌后部区域，评估指标包括：动物行为、体重和器官重量、血常规、组织损伤的血浆生化标志物以及炎性细胞因子水平和谱。为了评估对实验性感染的影响，采用了不同的方案（感染前和感染后）以及AWB给药时间（1至10天），同时使用异体全血（HWB）并评估血浆细胞因子谱。
在接受AWB治疗的健康小鼠中未观察到重大不良事件，除了在同一后肢接受三剂20μL AWB的动物出现步态障碍。AWB和SAL引发了即刻的多形核细胞反应，随后是单核细胞浸润。虽然SAL引发了炎症反应，但组织学特征和体液介质水平的动力学和强度与AWB不同，AWB引发的反应更早且更强烈，同时血浆IL-6升高。SAL的炎症峰值反应主要由含IL-10的单核细胞组成，在24小时时增强。根据急性感染小鼠模型，感染前后给予AWB和HWB仅使寄生虫血症水平略有降低（<30%），并未预防死亡。与未感染小鼠相比，所有感染动物在感染后第9天检测到IFN-γ、TNF-α和IL-6升高，但只有Bz组的TNF-α水平与感染未治疗小鼠相比有统计学显著降低（P<0.02）。
本研究表明，在所采用的急性模型中使用自体全血（AWB）无法降低感染小鼠的寄生虫负荷，仅使寄生虫血症水平略有降低（高达30%），但不能预防动物死亡。需要进一步研究以阐明该程序的有效影响。
