title: Preimplantation factor (PIF*) reverses neuroinflammation while promoting neural repair in EAE model.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah University Hospital Ein Kerem, Hebrew University, Jerusalem, Israel.
authors: Lola
authors: L
authors: Weiss
authors: Reuven
authors: R
authors: Or
authors: Richard C
authors: RC
authors: Jones
authors: Ravi
authors: R
authors: Amunugama
authors: Lellean
authors: L
authors: JeBailey
authors: Sivakumar
authors: S
authors: Ramu
authors: Steven A
authors: SA
authors: Bernstein
authors: Zhanna
authors: Z
authors: Yekhtin
authors: Osnat
authors: O
authors: Almogi-Hazan
authors: Reut
authors: R
authors: Shainer
authors: Israel
authors: I
authors: Reibstein
authors: Alexander O
authors: AO
authors: Vortmeyer
authors: Michael J
authors: MJ
authors: Paidas
authors: Michael
authors: M
authors: Zeira
authors: Shimon
authors: S
authors: Slavin
authors: Eytan R
authors: ER
authors: Barnea
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D005260:Female; D018836:Inflammation Mediators / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008815:Mice, Inbred Strains; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D009416:Nerve Regeneration / Q000187:drug effects* / Q000276:immunology; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D011897:Random Allocation
chemical_list: D018836:Inflammation Mediators; D010455:Peptides; C569738:preimplantation factor, synthetic