The Protective Effects of Lactoferrin Feeding against Endotoxin Lethal Shock in Germfree Piglets

The unique germfree, colostrum-deprived, immunologically “virgin” piglet model was used to evaluate the ability of lactoferrin (LF) to protect against lethal shock induced by intravenously administered endotoxin. Piglets were fed LF or bovine serum albumin (BSA) prior to challenge with intravenous Escherichia coli lipopolysaccharide (LPS), and temperature, clinical symptoms, and mortality were tracked for 48 h following LPS administration. Prefeeding with LF resulted in a significant decrease in piglet mortality compared to feeding with BSA (16.7 versus 73.7% mortality, P < 0.001). Protection against the LPS challenge by LF was also correlated with both resistance to induction of hypothermia by endotoxin and an overall increase in wellness, as quantified by a toxicity score developed for these studies. In vitro studies using a flow cytometric assay system demonstrated that LPS binding to porcine monocytes was inhibited by LF in a dose-dependent fashion, suggesting that the mechanism of LF action in vivo may be inhibition of LPS binding to monocytes/macrophages and, in turn, prevention of induction of monocyte/macrophage-derived inflammatory-toxic cytokines.

本研究采用独特的无菌、无初乳且免疫未致敏仔猪模型，评估乳铁蛋白（lactoferrin, LF）对抗静脉注射内毒素诱导致死性休克的能力。仔猪在接受大肠杆菌脂多糖（LPS）攻毒前，分别饲喂LF或牛血清白蛋白（BSA），并在LPS给药后48小时内持续监测体温、临床症状与死亡率。与饲喂牛血清白蛋白组相比，预饲喂乳铁蛋白可显著降低仔猪死亡率（两组死亡率分别为16.7%与73.7%，P < 0.001）。乳铁蛋白对LPS攻毒的保护作用，还与抵抗内毒素诱导的低体温症以及整体健康状态改善显著相关，该健康状态通过本研究开发的毒性评分进行量化。体外流式细胞术检测实验表明，LF可通过剂量依赖性方式抑制LPS与猪单核细胞的结合，提示LF在体内的作用机制可能为阻断LPS与单核细胞/巨噬细胞的结合，进而防止单核细胞/巨噬细胞源性炎性毒性细胞因子的诱导产生。