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血清衍生转移因子刺激先天免疫系统以改善高风险病原体情况下的生存特征。

Serum Derived Transfer Factor Stimulates the Innate Immune System to Improve Survival Traits in High Risk Pathogen Scenarios.

作者信息

Willeford Bridget V, Shapiro-Dunlap Trudy, Willeford Kenneth O

机构信息

Laboratory Animal Resources and Care, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, 39762.

Collierville Animal Clinic, Collierville, TN, 38017.

出版信息

Drug Dev Res. 2017 Aug;78(5):189-195. doi: 10.1002/ddr.21392. Epub 2017 Jun 22.

Abstract

Preclinical Research Transfer Factors (TFs) are low molecular weight (<5,000 daltons) biological response mediators. In the present study, a serum derived TF improved the ability of the recipient animal to survive high-risk infectious challenges (salmonellosis and canine parvoviral enteritis (CPV)) by altering the host's cytokine response profile. Mice mortally challenged with 5,000 colony-forming units of Salmonella experienced a group mortality of 73% while mice treated with a single 5 mg dose of the TF demonstrated a significant decrease in morbidity (7%, p ≤ 0.01). The splenic bacterial load in untreated mice was over 10,000 times higher than that in the TF treated mice. Twenty-four hours post-administration, the treated murine population expressed a rapid temporal increase in serum IL-6 (26-fold) and INF-γ (77-fold) concentrations. IL-6 can act as a critical signal regulating action against bacterial pathogens. A comparative double-blind study performed using dogs confirmed to be undergoing a canine parvovirus challenge showed that when conventional supportive therapy was supplemented with a single 5 mg TF dose there was a reduction (p ≤ 0.01) in group mortality (68% of the TF treated group survived versus 32% of the placebo group), an observation consistent with the observed increase in INF-γ, a cytokine associated with promoting antiviral activity. Drug Dev Res 78 : 189-195, 2017. © 2017 Wiley Periodicals, Inc.

摘要

临床前研究 转移因子(TFs)是低分子量(<5000道尔顿)的生物反应介质。在本研究中,一种血清来源的TF通过改变宿主的细胞因子反应谱,提高了受体动物在面临高风险感染挑战(沙门氏菌病和犬细小病毒肠炎(CPV))时的生存能力。用5000个沙门氏菌菌落形成单位进行致命攻击的小鼠,群体死亡率为73%,而用单一5mg剂量的TF治疗的小鼠发病率显著降低(7%,p≤0.01)。未治疗小鼠的脾脏细菌载量比TF治疗小鼠高10000倍以上。给药后24小时,治疗组小鼠血清IL-6(26倍)和INF-γ(77倍)浓度迅速随时间增加。IL-6可作为对抗细菌病原体的关键调节信号。一项针对确诊感染犬细小病毒的犬进行的比较双盲研究表明,当常规支持治疗辅以单一5mg TF剂量时,群体死亡率降低(p≤0.01)(TF治疗组68%存活,而安慰剂组为32%),这一观察结果与观察到的与促进抗病毒活性相关的细胞因子INF-γ增加一致。药物研发研究78:189 - 195,2017年。©2017威利期刊公司

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a973/5600497/4d77d727b7ff/nihms884838f1.jpg

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