Williams A S, Camilleri J P, Topley N, Williams B D
Department of Rheumatology, University of Wales College of Medicine Cardiff, U.K.
J Pharmacol Toxicol Methods. 1994 Sep;32(1):53-8. doi: 10.1016/1056-8719(94)90018-3.
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.
在正常和患有关节炎的大鼠体内，研究了一种含有甲氨蝶呤磷脂共轭物的新型脂质体制剂（MTX-LIPO）对巨噬细胞介质释放的影响。从经MTX-LIPO处理的关节炎大鼠中分离出的腹腔巨噬细胞，用脂多糖刺激后，与从生理盐水处理的对照组中分离出的巨噬细胞相比，产生的肿瘤坏死因子（TNF）和前列腺素（PGE2）明显更少。在同一实验系统中，游离甲氨蝶呤仅抑制前列腺素释放，但在这方面比MTX-LIPO更有效。目前正在进行进一步研究，以调查MTX-LIPO和MTX治疗对脂多糖诱导的体内各种促炎介质血浆水平升高的影响。在用游离MTX治疗的大鼠血液中显示出造血毒性，其特征是与MTX-LIPO和生理盐水处理的大鼠相比，网织红细胞计数显著降低。
