Effects of liposteroid on skin lesions in autoimmune MRLlpr/lpr mice.
Dexamethasone palmitate (D-PAL) incorporated into lipid microspheres (D-PAL emulsion) is taken up by the reticuloendothelial system and by some inflammatory cells. Therefore, it has a stronger anti-inflammatory activity than free corticosteroids in vivo. To study the effect of D-PAL emulsion on systemic lupus erythematosus (SLE), we administered D-PAL emulsion to MRLlpr/lpr mice, an animal model for human SLE. The effect of D-PAL emulsion was compared with that of methylprednisolone (m-PSL), a water-soluble steroid. Percent survival was higher in the group treated with 0.25 mg of D-PAL emulsion intravenously once every 4 weeks than in those groups treated similarly with m-PSL or PBS control. Swelling of lymph nodes was frequent in the group treated with m-PSL or with PBS, while rarely observed in the group treated with D-PAL emulsion. Proteinuria was more frequent in the groups treated with m-PSL or PBS than in the group treated with D-PAL emulsion. Although the frequency of skin lesions was not different between these three groups, the control and m-PSL treated mice had severe skin lesions, such as hair loss of erythematous skin with scales and crusts at the nape, while D-PAL emulsion treated animals showed only facial alopecia without inflammatory skin changes. These data demonstrate that D-PAL emulsion was more effective than a corresponding dose of m-PSL on autoimmune prone mice. This suggests that intermittent administration of D-PAL emulsion may be effective in the treatment of human SLE.
Aihara
M
M
Department of Dermatology, Yokohama City University School of Medicine, Japan.
Aihara
Y
Y
Takahashi
Y
Y
Nakajima
H
H
D000818:Animals; D015551:Autoimmunity / Q000276:immunology; D003907:Dexamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004655:Emulsions; D005260:Female; D008081:Liposomes; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008775:Methylprednisolone / Q000008:administration & dosage; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008863:Microspheres; D012995:Solubility
D004655:Emulsions; D008081:Liposomes; C035081:dexamethasone 21-palmitate; D003907:Dexamethasone; D008775:Methylprednisolone