title: Treatment of established collagen induced arthritis with prostaglandin E1 incorporated in lipid microspheres.
abstract: OBJECTIVE
  In view of evidence obtained from in vitro and in vivo experiments that prostaglandin E1 (PGE1) has regulatory effects on disordered immune responses and inflammation, we investigated whether lipo-PGE1, an efficient drug delivery system incorporating PGE1 into lipid microspheres, can ameliorate arthritis in the collagen induced arthritis (CIA) model of rheumatoid arthritis (RA).
  
  
  METHODS
  DBA/1J male mice were immunized with bovine type II collagen in adjuvant, and treated daily from onset of clinical arthritis with intravenous administration of lipo-PGE1 (5-50 microg/kg) or lipid vehicle as a control. Arthritis was assessed over a 10 day treatment period by monitoring for paw swelling and clinical score. Histopathology of the arthritic hind paws was also evaluated. Lipo-PGE1 accumulation in arthritic joint tissues was measured using 3H labeled PGE1 incorporated in lipid microspheres.
  
  
  RESULTS
  Arthritis was significantly suppressed in lipo-PGE1 treated mice compared with lipid vehicle treated controls (p < 0.05, p < 0.016, respectively) in a dose-dependent manner. Histopathological assessment showed a significant reduction of pannus formation and joint destruction in lipo-PGE1 treated mice compared with controls (p < 0.05). Lipo-PGE1 preferentially accumulated in arthritic joints for a longer period than free PGE1.
  
  
  CONCLUSIONS
  Using an efficient drug delivery system, PGE1 can suppress CIA, and lipo-PGE1 may have a potential therapeutic role in RA.
authors.affiliation: Department of Internal Medicine, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Moriuchi-Murakami
authors.forename: H
authors.initials: H
authors.lastname: Yamada
authors.forename: O
authors.initials: O
authors.lastname: Ishii
authors.forename: T
authors.initials: T
authors.lastname: Kikukawa
authors.forename: R
authors.initials: R
authors.lastname: Igarashi
mesh_terms: D000527:Alprostadil / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D015519:Bone Density; D002417:Cattle; D003094:Collagen / Q000097:blood / Q000276:immunology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006614:Hindlimb / Q000187:drug effects / Q000473:pathology; D007596:Joints / Q000187:drug effects / Q000473:pathology; D008081:Liposomes; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008863:Microspheres; D013977:Tibia / Q000187:drug effects / Q000378:metabolism; D014316:Tritium
chemical_list: D008081:Liposomes; D014316:Tritium; D003094:Collagen; D000527:Alprostadil