Intravenous liposomal prednisolone downregulates in situ TNF-alpha production by T-cells in experimental autoimmune encephalomyelitis.
Multiple sclerosis (MS) relapses are treated with high-dose IV glucocorticosteroids. Here we investigated mechanisms of long-circulating polyethylene glycol-coated liposomes encapsulating prednisolone (PL) in adoptive transfer experimental autoimmune encephalomyelitis. Rats received IV 10 mg/kg PL 6, 18, or 42 hr before sacrifice at disease maximum. In formalin-fixed, paraffin-embedded spinal cord we employed a nonfluorescent immunohistochemical (IHC) double labeling. We stained for tumor necrosis factor-alpha (TNF-alpha) in combination with a T-cell antigen. Compared with PBS-containing liposomes, PL at 18 hr, and more at 42 hr, significantly reduced the rate of TNF-alpha double-labeled T-cells. This correlated with an ameliorated disease score at day 5 after PL 42 hr. Our results help to further understand mechanisms of action of drug targeting by liposomal steroids, with possible implications for treatment of autoimmune disorders such as MS.
Schmidt
Jens
J
Department of Neurology, University of Würzburg, Würzburg, Germany. schmidtj@ninds.nih.gov
Metselaar
Josbert M
JM
Gold
Ralf
R
D000818:Animals; D015536:Down-Regulation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D008081:Liposomes; D011092:Polyethylene Glycols; D011239:Prednisolone / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D008081:Liposomes; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols; D011239:Prednisolone