The influence of anti-rheumatic drugs on hepatic mRNA levels of acute-phase proteins in rats with adjuvant arthritis.
Using specific cDNA probes, we have investigated drug-induced changes in hepatic mRNA levels of the major acute-phase proteins (APP) fibrinogen, alpha 2-macroglobulin (alpha 2-MG), albumin and alpha 1-acid glycoprotein (alpha 1-AGP) in male Lewis rats with adjuvant arthritis. Test compounds were given orally from day 0 to 20 and hepatic mRNA analysis was performed at day 21. Prednisolone (1, 3, 10 mg/kg), Cyclosporine A (1, 3, 10 mg/kg) and cyclophosphamide (3 mg/kg) dose-dependently normalized hepatic mRNA levels of all four APP. Equipotent anti-inflammatory doses of indomethacin (0.3, 1 mg/kg) significantly downregulated alpha 2-MG mRNA levels but were much less effective in influencing albumin and alpha 1-AGP mRNA levels and even slightly increased hepatic fibrinogen mRNA levels. These results suggest that cytokine over-production, which is thought to be responsible for the acute-phase response in rats with adjuvant arthritis, can be effectively downregulated by immunosuppressive drugs, but is distinctly less affected by the cyclooxygenase inhibitor indomethacin.
Geiger
T
T
Research Department, Ciba-Geigy Ltd., Basel, Switzerland.
Jagher
B
B
Pignat
W
W
Tscherry
B
B
Wiesenberg
I
I
D000209:Acute-Phase Proteins / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D003520:Cyclophosphamide / Q000627:therapeutic use*; D016572:Cyclosporine / Q000627:therapeutic use*; D015536:Down-Regulation / Q000187:drug effects; D007213:Indomethacin / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011239:Prednisolone / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew
D000209:Acute-Phase Proteins; D012333:RNA, Messenger; D016572:Cyclosporine; D003520:Cyclophosphamide; D011239:Prednisolone; D007213:Indomethacin