Prostaglandin and tumor necrosis factor secretion by peritoneal macrophages isolated from normal and arthritic rats treated with liposomal methotrexate.
The effect of a novel liposomal preparation containing a phospholipid conjugate of methotrexate (MTX-LIPO) upon macrophage mediator release was investigated in normal and arthritic rats ex vivo. Peritoneal macrophages isolated from MTX-LIPO-treated arthritic rats and stimulated with lipopolysaccharide produced significantly less tumor necrosis factor (TNF) and prostaglandin (PGE2) than did macrophages isolated from saline-treated controls. In the same experimental system, free methotrexate only inhibited prostaglandin release, but it was more potent than MTX-LIPO in this respect. Additional studies are presently underway to investigate the effect of MTX-LIPO and MTX treatment upon the lipopolysaccharide-induced rise in plasma levels of various proinflammatory mediators in vivo. Haematopoietic toxicity was demonstrated in blood isolated from rats treated with free MTX, and this was as characterized by a significant reduction in reticulocyte count compared with MTX-LIPO and saline-treated rats.
Department of Rheumatology, University of Wales College of Medicine Cardiff, U.K.
A S
AS
Williams
J P
JP
Camilleri
N
N
Topley
B D
BD
Williams
D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D015232:Dinoprostone / Q000378:metabolism*; D004337:Drug Carriers; D008070:Lipopolysaccharides / Q000494:pharmacology; D008081:Liposomes; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D010714:Phosphatidylethanolamines / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D004337:Drug Carriers; D008070:Lipopolysaccharides; D008081:Liposomes; D010714:Phosphatidylethanolamines; D014409:Tumor Necrosis Factor-alpha; C047978:methotrexate-gamma-1,2-dimyristoylphosphatidylethanolamine; D015232:Dinoprostone; D008727:Methotrexate