THE INFLUENCE OF ANTIRHEUMATIC DRUGS ON HEPATIC MESSENGER-RNA 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) fibrino gen, alpha2-macroglobulin (alpha2-MG), albumin and alpha1-acid glycopr otein (alpha1-AGP) in male Lewis rats with adjuvant arthritis. Test co mpounds were given orally from day 0 to 20 and hepatic mRNA analysis w as performed at day 21. Prednisolone (1, 3, 10 mg/kg), Cyclosporine A (1, 3, 1 0 mg/kg) and cyclophosphamide (3 mg/kg) dose-dependently norm alized hepatic mRNA levels of all four APP. Equipotent anti-inflammato ry doses of indomethacin (0.3, 1 mg/kg) significantly downregulated al pha2-MG mRNA levels but were much less effective in influencing albumi n and alpha1-AGP mRNA levels and even slightly increased hepatic fibri nogen mRNA levels. These results suggest that cytokine over-production , which is thought to be responsible for the acute-phase response in r ats with adjuvant arthritis, can be effectively downregulated by immun osuppressive drugs, but is distinctly less affected by the cyclooxygen ase inhibitor indomethacin.