PROSTAGLANDIN AND TUMOR-NECROSIS-FACTOR SECRETION BY PERITONEAL-MACROPHAGES ISOLATED FROM NORMAL AND ARTHRITIC RATS TREATED WITH LIPOSOMAL METHOTREXATE

Authors
WILLIAMS AS CAMILLERI JP TOPLEY N WILLIAMS BD
Citation
As. Williams et al., PROSTAGLANDIN AND TUMOR-NECROSIS-FACTOR SECRETION BY PERITONEAL-MACROPHAGES ISOLATED FROM NORMAL AND ARTHRITIC RATS TREATED WITH LIPOSOMAL METHOTREXATE, Journal of pharmacological and toxicological methods, 32(1), 1994, pp. 53-58
Citations number
41
Categorie Soggetti
Toxicology,"Pharmacology & Pharmacy
Journal title
Journal of pharmacological and toxicological methods → ACNP
ISSN journal
10568719
Volume
32
Issue
1
Year of publication
1994
Pages
53 - 58
Database
ISI
SICI code
1056-8719(1994)32:1<53:PATSBP>2.0.ZU;2-P
Abstract
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 macr ophages isolated from MTX-LIPO-treated arthritic rats and stimulated w ith lipopolysaccharide produced significantly less tumor necrosis fact or (TNF) and prostaglandin (PGE(2)) than did macrophages isolated from saline-treated controls. In the same experimental system, free methot rexate only inhibited prostaglandin release, but it was more potent th an MTX-LIPO in this respect. Additional studies an presently underway to investigate the effect of MTX-LIPO and MTX treatment upon the lipop olysaccharide-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 characterize d by a significant reduction in reticulocyte count compared with MTX-L IPO and saline-treated rats.