Latex proteins downregulate inflammation and restores blood-coagulation homeostasis in acute Salmonella infection

BACKGROUND Calotropis procera latex protein fraction (LP) was previously shown to protect animals from septic shock. Further investigations showed that LP modulate nitric oxide and cytokines levels. OBJECTIVES To evaluate whether the protective effects of LP, against lethal bacterial infection, is observed in its subfractions (LPPII and LPPIII). METHODS Subfractions (5 and 10 mg/kg) were tested by i.p. administration, 24 h before challenging with lethal injection (i.p.) of Salmonella Typhimurium. LPPIII (5 mg/kg) which showed higher survival rate was assayed to evaluate bacterial clearance, histopathology, leukocyte recruitment, plasma coagulation time, cytokines and NO levels. FINDINGS LPPIII protected 70% of animals of death. The animals given LPPIII exhibited reduced bacterial load in blood and peritoneal fluid after 24 h compared to the control. LPPIII promoted macrophage infiltration in spleen and liver. LPPIII restored the coagulation time of infected animals, increased IL-10 and reduced NO in blood. MAIN CONCLUSIONS LPPIII recruited macrophages to the target organs of bacterial infection. This addressed inflammatory stimulus seems to reduce bacterial colonisation in spleen and liver, down regulate bacterial spread and contribute to avoid septic shock.

背景：牛角瓜（Calotropis procera）胶乳蛋白组分（LP）此前已被证实可使实验动物免受脓毒性休克（septic shock）的侵害。后续研究进一步发现，LP可调控一氧化氮（nitric oxide）与细胞因子（cytokines）的水平。
目的：旨在探究LP对抗致死性细菌感染的保护作用是否可在其亚组分（LPPII与LPPIII）中重现。
方法：以5 mg/kg与10 mg/kg的剂量通过腹腔内（intraperitoneal, i.p.）注射给予各亚组分，于给药24小时后，以致死剂量的鼠伤寒沙门氏菌（Salmonella Typhimurium）行腹腔内注射感染造模。针对存活率更高的LPPIII（5 mg/kg）给药组，进一步检测其细菌清除能力、组织病理学变化、白细胞招募情况、血浆凝血时间、细胞因子及一氧化氮水平。
结果：LPPIII可使70%的实验动物免于死亡。与对照组相比，给予LPPIII的实验动物在感染24小时后，其血液与腹腔液中的细菌载量显著降低。LPPIII可促进脾脏与肝脏组织中的巨噬细胞浸润。LPPIII可恢复感染动物的血浆凝血时间，升高血液中IL-10的水平并降低一氧化氮含量。
主要结论：LPPIII可将巨噬细胞招募至细菌感染的靶器官。这种针对性的炎症刺激似乎可降低脾脏与肝脏中的细菌定植量，抑制细菌扩散，并有助于避免脓毒性休克的发生。