RP 54745, a potential antirheumatic compound. I. Inhibitor of macrophage stimulation and interleukin-1 production.
RP 54745 is an amino-dithiole-one compound found to be active at micromolar concentration on the metabolism of stimulated macrophages, for example, the hexose monophosphate pathway (HMP) and the exocytosis of lysosomal enzymes. LPS-induced interleukin-1 (IL-1) production by murine peritoneal macrophages was also diminished by this compound in vitro as well as in vivo. This effect was confirmed at the mRNA level; at the concentration of 3 x 10(-6) M, the IL-1 alpha and beta mRNA signals were inhibited, whereas the TNF alpha mRNA signal was only slightly lessened. These observations were confirmed in vivo, with a dose of RP 54745 of 25 mg kg-1. These results led us to consider that RP 54745 might influence certain cells and cytokines implicated in the regulation of the immune system, the disfunctioning of which can lead to inflammatory disorders or autoimmune pathologies.
Folliard
F
F
Rhône-Poulenc Rorer, Centre de Recherche de Vitry-Alfortville, Vitry sur Seine, France.
Bousseau
A
A
Terlain
B
B
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D005966:Glucuronidase / Q000378:metabolism; D007202:Indicators and Reagents; D007375:Interleukin-1 / Q000096:biosynthesis*; D007546:Isoquinolines / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008262:Macrophage Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D010427:Pentose Phosphate Pathway / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007202:Indicators and Reagents; D007375:Interleukin-1; D007546:Isoquinolines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C077452:RP 54745; D005966:Glucuronidase