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The influence of anti-rheumatic drugs on hepatic mRNA levels of acute-phase proteins in rats with adjuvant arthritis

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Abstract

Using specific cDNA probes, we have investigated drug-induced changes in hepatic mRNA levels of the major acute-phase proteins (APP) fibrinogen, α2-macroglobulin (α2-MG), albumin and α1-acid glycoprotein (α1-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 α2-MG mRNA levels but were much less effective in influencing albumin and α1-AGP mRNA levels and even slightly increased hepatic fibrinogen mRNA levels. These results suggest that cytokine overproduction, 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.

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Authors and Affiliations

  1. Research Department, Pharmaceuticals Division, Ciba-Geigy Ltd., Basel, Switzerland

    T. Geiger, B. Jagher, W. Pignat, B. Tscherry & I. Wiesenberg

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  1. T. Geiger
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  2. B. Jagher
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  3. W. Pignat
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  4. B. Tscherry
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  5. I. Wiesenberg
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Geiger, T., Jagher, B., Pignat, W. et al. The influence of anti-rheumatic drugs on hepatic mRNA levels of acute-phase proteins in rats with adjuvant arthritis. Agents and Actions 38 (Suppl 2), C69–C72 (1993). https://doi.org/10.1007/BF01991141

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