Willeford Bridget V, Shapiro-Dunlap Trudy, Willeford Kenneth O
Laboratory Animal Resources and Care, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, 39762.
Collierville Animal Clinic, Collierville, TN, 38017.
Drug Dev Res. 2017 Aug;78(5):189-195. doi: 10.1002/ddr.21392. Epub 2017 Jun 22.
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.
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