Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah University Hospital Ein Kerem, Hebrew University, Jerusalem, Israel.
J Neurol Sci. 2012 Jan 15;312(1-2):146-57. doi: 10.1016/j.jns.2011.07.050. Epub 2011 Oct 13.
Embryo-derived PIF modulates systemic maternal immunity without suppression. Synthetic analog (sPIF) prevents juvenile diabetes, preserves islet function, reducing oxidative stress/protein misfolding. We investigate sPIF effectiveness in controlling neuroinflammation/MS.
Examine sPIF-induced protection against harsh, clinical-relevant murine EAE-PLP acute and chronic models. Evaluate clinical indices: circulating cytokines, spinal cord histology, genome, canonical global proteome, cultured PLP-activated splenocytes cytokines, and immunophenotype.
Short-term, low-dose sPIF prevented paralysis development and lowered mortality (P<0.05). Episodic sPIF reversed chronic paralysis (P<0.0001) completely in >50%, by day 82. Prevention model: 12days post-therapy, sPIF reduced circulating IL12 ten-fold and inflammatory cells access to spinal cord. Regression model: sPIF blocked PLP-induced IL17 and IL6 secretions. Long-term chronic model: sPIF reduced spinal cord pro-inflammatory cytokines/chemokines, (ALCAM, CF1, CCL8), apoptosis-promoters, inflammatory cells access (JAM3, OPA1), solute channels (ATPases), aberrant coagulation factors (Serpins), and pro-antigenic MOG. Canonical proteomic analysis demonstrated reduced oxidative phosphorylation, vesicle traffic, cytoskeleton remodeling involved in neuro-cytoskeleton breakdown (tubulins), associated with axon re-assembly by (MTAPs)/improved synaptic transmission.
sPIF--through coordinated central and systemic multi-targeted action--reverses neuroinflammation/MS and imparts significant neuroprotective effects up to total paralysis resolution. Clinical testing is warranted and planned.
胚胎衍生的 PIF 调节全身母性免疫而不抑制。合成类似物（sPIF）可预防青少年糖尿病，维持胰岛功能，减少氧化应激/蛋白质错误折叠。我们研究了 sPIF 在控制神经炎症/MS 中的有效性。
研究 sPIF 对苛刻的、临床相关的鼠 EAE-PLP 急性和慢性模型的保护作用。评估临床指标：循环细胞因子、脊髓组织学、基因组、典型的全基因组蛋白组、培养的 PLP 激活脾细胞细胞因子和免疫表型。
短期、低剂量的 sPIF 可预防瘫痪的发展和降低死亡率（P<0.05）。间歇性 sPIF 完全逆转了慢性瘫痪（P<0.0001），在>50%的病例中，在第 82 天。预防模型：治疗后 12 天，sPIF 将循环中的 IL12 降低十倍，并减少炎症细胞进入脊髓。回归模型：sPIF 阻断了 PLP 诱导的 IL17 和 IL6 分泌。长期慢性模型：sPIF 降低了脊髓中的促炎细胞因子/趋化因子（ALCAM、CF1、CCL8）、凋亡促进剂、炎症细胞进入（JAM3、OPA1）、溶质通道（ATPases）、异常凝血因子（Serpins）和前抗原性 MOG。经典蛋白质组学分析表明，氧化磷酸化、囊泡运输、细胞骨架重塑减少，与神经细胞骨架断裂（微管蛋白）有关，同时与轴突重新组装（MTAPs）/改善突触传递有关。
sPIF--通过协调中枢和全身多靶点作用--逆转神经炎症/MS 并产生显著的神经保护作用，直至完全瘫痪缓解。需要并计划进行临床测试。
