title: Phosphatidylserine, a putative inhibitor of tumor necrosis factor, prevents autoimmune demyelination.
abstract: We tested the effect of bovine cortex phosphatidylserine (BC-PS), a membrane phospholipid known to inhibit the release of the cytokine tumor necrosis factor (TNF), in SJL/J mice sensitized for adoptively transferred experimental autoimmune encephalomyelitis (EAE). Control, sensitized mice developed severe clinical and histologic EAE within 6 to 9 days, whereas only 20% of mice given BC-PS displayed clinical signs that were much less severe and minimal CNS pathology. Cessation of BC-PS treatment after 15 to 40 days led to disease within 1 to 2 weeks, but when treatment was more prolonged, animals remained healthy after cessation. Serial transfer of spleen cells (SC) from BC-PS-treated and control animals into naive recipients resulted in acute EAE within 6 to 7 days with cells from either donor type. Animals treated late with BC-PS failed to relapse and generally remained healthier than controls did over a 40-day period of observation. Cultures of lymph node cells or SC from BC-PS-treated and control animals showed an 80 to 90% reduction in TNF production in the BC-PS-treated group. Thus, we demonstrate that PS can abrogate or significantly reduce the severity of EAE without permanently inhibiting effector T cells. The approach might be considered a candidate for future therapies of relevance to MS.
authors.affiliation: Department of Pathology (Neuropathology), Albert Einstein College of Medicine, Bronx, NY 10461.
authors.forename: G
authors.initials: G
authors.lastname: Monastra
authors.forename: A H
authors.initials: AH
authors.lastname: Cross
authors.forename: A
authors.initials: A
authors.lastname: Bruni
authors.forename: C S
authors.initials: CS
authors.lastname: Raine
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000517:prevention & control*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D051379:Mice; D010718:Phosphatidylserines / Q000494:pharmacology*; D013116:Spinal Cord / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D010718:Phosphatidylserines; D014409:Tumor Necrosis Factor-alpha