Treatment of established collagen induced arthritis with prostaglandin E1 incorporated in lipid microspheres.
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.
Moriuchi-Murakami
E
E
Department of Internal Medicine, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Japan.
Yamada
H
H
Ishii
O
O
Kikukawa
T
T
Igarashi
R
R
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
D008081:Liposomes; D014316:Tritium; D003094:Collagen; D000527:Alprostadil