Skip to main content
Log in

Meloxicam: A potent inhibitor of adjuvant arthritis in the Lewis rat

  • Published:
Inflammation Research Aims and scope Submit manuscript

Abstract

The effects of meloxicam, piroxicam, diclofenac and tenidap on the swelling of hind paws, radiologically-detectable bone and cartilage destruction of hind paws, increase in spleen weight, increase in erythrocyte sedimentation rate and changes in serum protein composition in male Lewis rats with adjuvant arthritis were studied following once-daily oral administration of these drugs for 21 days. All the drugs dose-dependently inhibited hind paw swelling. For equal activity against hind paw swelling caused by the secondary reaction, the required daily dose of piroxicam was about twice that of meloxicam; those of diclofenac and tenidap were about 3.5 and 60 times higher respectively. The bone and cartilage destruction induced by adjuvant arthritis were inhibited by meloxicam at low daily doses and by piroxicam at doses approximately four times those of meloxicam. Diclofenac and tenidap had only a weak effect on radiologically-detectable lesions when administered at doses sufficient to reduce paw swelling. Meloxicam also had a dose-dependent corrective effect on the systemic changes which occur in adjuvant arthritic rats, e.g. increase in spleen weight, increase in erythrocyte sedimentation rate and changes in serum protein composition. Piroxicam produced similar effects, at 3–4 times higher doses. Diclofenac and tenidap did not show comparable effects when administered at appropriate doses. These findings indicate that the action of meloxicam and piroxicam differs from that of diclofenac and tenidap in adjuvant arthritis in the Lewis rat. At oral doses which significantly reduce edema formation, only meloxicam and piroxicam showed a significant effect on systemic parameters of adjuvant disease in the Lewis rat.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Stoerk HC, Bielinski LC, Budzilovich T. Chronic polyarthritis in rats injected with spleen in adjuvants. Am J Path 1954;30:616.

    Google Scholar 

  2. Pearson CM. Development of arthritis, periarthritis and periostitis in rats given adjuvants. Proc Soc Exp Biol NY 1956;91:95–101.

    Google Scholar 

  3. Pearson CM. Arthritis in animals. In: McCarty DJ, editors. Arthritis and Allied Conditions. 9th ed. Philadelphia: Lea and Febinger, 1979:308–19.

    Google Scholar 

  4. Whitehouse DJ, Whitehouse MW, Pearson CM. Passive transfer of adjuvant induced arthritis and allergic encephalomyelitis in rats using thoracic duct lymphocytes. Nature 1969;224:1322.

    PubMed  Google Scholar 

  5. Pearson CM, Wood FD. Passive transfer of adjuvant arthritis by lymph node or spleen cells. J Exp Med 1964;120:547–60.

    PubMed  Google Scholar 

  6. Burstein NA, Waksman BH. The pathogenesis of adjuvant disease in the rat. Yale J Biol Med 1964;36:177–94.

    Google Scholar 

  7. Pearson CM, Wood FD. Studies of arthritis and other lesions induced in rats by the injection of mycobacterial adjuvant. Am J Pathol 1963;42:73–6.

    PubMed  Google Scholar 

  8. Mohr W, Wild A, Beneke G. Chronische Osteoarthritis als Manifestation der Adjuvanskrankheit der Ratte. Beitr Pathol 1974;153:1–17.

    PubMed  Google Scholar 

  9. Mohr W, Wild A, Wolf HP. Untersuchungen zur Pathogenese der entzündlichen Knorpelzerstörung bei der Adjuvansarthritis der Ratte. Z Rheumatol 1980;39:212–20.

    PubMed  Google Scholar 

  10. Blackham A, Burns JW, Farmer JB, Radziwonik H, Westwick J. An X-ray analysis of adjuvant arthritis in the rat. The effective of prednisolone and indomethacin. Agents Actions 1977;7:145–51.

    PubMed  Google Scholar 

  11. Benslay DN, Nickander R. Comparative effects of benoxaprofen and other anti-inflammatory drugs on done damage in the adjuvant arthritic rat. Agents Actions 1982;12:313–9.

    PubMed  Google Scholar 

  12. Glenn EM, Gray J, Kooyers W. Chemical changes in adjuvantinduced polyarthritis in rats. Am J Vet Res 1965;26:1195–203.

    PubMed  Google Scholar 

  13. Piliero SJ, Graeme MC, Sigg EB, Chinea G, Colombo C. Action of anti-inflammatory agents upon blood and histo-pathologic changes induced by periarthritis in rats. Life Sci 1966;5:1057–69.

    PubMed  Google Scholar 

  14. Lowe JS. Serum protein changes in rats with arthritis induced by mycobacterial adjuvant. Biochem Pharmacol 1964;13:633–41.

    PubMed  Google Scholar 

  15. Glenn EM, Bowman, NBJ, Koslowske TC. The systemic response to inflammation. Biochem Pharmacol 1968;Suppl:27–9.

    Google Scholar 

  16. Katz L, Piliero SJ. A study of adjuvant induced polyarthritis in the rat with special reference to associated immunological phenomena. Ann NY Acad Sci 1969;147:515–6.

    Google Scholar 

  17. Stecher VI, Kaplan JE, Connolly K, Mielens Z, Saelens JK. Fibronectin in acute and chronic inflammation. Arthr Rheum 1986;29:394–9.

    Google Scholar 

  18. Schade R, Gohler K, Burger W, Hirschelmann R. Modulation of rat C-reactive protein serum level by dexamethasone and adrenaline — comparison with response ofα 2-acute phase globulin. Agents Actions 1987;22:280–7.

    PubMed  Google Scholar 

  19. Bürger W, Schade R, Hirschelmann R. The rat C-reactive protein-isolation and response to experimental inflammation and tissue damage. Agents Actions 1987;21:93–7.

    PubMed  Google Scholar 

  20. Connolly K, Stecher VJ, Danis E, Pruden DJ, La Brie T. Alteration of interleukin-activity and the acute phase response in adjuvant arthritis rats treated with disease modifying antirheumatic drugs. Agents Actions 1988;25:94–105.

    PubMed  Google Scholar 

  21. DeBeer RFC, Baltz ML, Munn EA, Feinstein A, Taylor J, Bruton C, et al. Isolation and characterization of C-reactive protein and serum amyloid P component in the rat. Immunol 1982:45:55–70.

    Google Scholar 

  22. Otterness JG, Pazoles PP, Moore PE, Pepys MB. C-reactive protein as an index of disease activity. Comparison of tenidap, cyclophosphamide and hexamethasone in rat adjuvant arthritis. J Rheumatol 1991;18:505–11

    PubMed  Google Scholar 

  23. Trentham DE, McClure MW, Susman P, David JR. Auto-immunity to collagen in adjuvant arthritis in rats. J. Clin Invest 1980;66:1109–12.

    PubMed  Google Scholar 

  24. Rosenthale ME, Nagra CL. Comparative effects of some immuno-suppressive and antiinflammatory drugs on allergic encephalomyelitis and adjuvant arthritis. Proc Soc Exp Biol Med 1967;125:149–54.

    PubMed  Google Scholar 

  25. Whitehouse MW, Beck FW. Standardization of arthritogenic adjuvants for evaluating anti-inflammatory and immunosuppressant drugs. Agents Actions 1974;4:227–9.

    PubMed  Google Scholar 

  26. Engelhardt G, Homma D, Schlegel K, Schnitzler C. Anti-inflammatory, analgesic, antipyretic and related properties of meloxicam, a new non-steroid antiinflammatory agent. Inflamm Res 1995;44:423–33.

    PubMed  Google Scholar 

  27. Engelhardt G. Meloxicam inhibits preferentially COX-2. Eur J Clin Pharmacol 1994;47:A98.

    Google Scholar 

  28. Engelhardt G, Pairet M. A new NSAID with an improved safety profile through preferential inhibition of COX-2. Rheumatol Eur 1995;24(Suppl 3):272.

    Google Scholar 

  29. Lund B, Distel M, Bluhmki E. A double-blind, placebo controlled study of three different doses of meloxicam in patients with osteoarthritis of the knee. Scand J Rheumatol 1994;98:A117.

    Google Scholar 

  30. Huskisson EC, Narjes H, Bluhmki E. Efficacy and tolerance of meloxicam, a new NSAID, in dialy oral doses of 15, 30 and 60 mg in comparison to 20 mg piroxicam in patients with rheumatoid arthritis. Scand J Rheumatol 1994;98:A115.

    Google Scholar 

  31. Lemmel EM. A placebo controlled double blind clinical trial of 7.5 mg and 15 mg of meloxicam in short term treatment of patients with rheumatoid arthritis (RA). Eur J Clin Pharmacol 1995;47:A105.

    Google Scholar 

  32. Garland LG, Smith SJ, Sim MF. A device for the rapid measurement of rat foot volume. J Pharm Pharmacol 1968;20:236–8.

    PubMed  Google Scholar 

  33. Linder A. Statistische Methoden. 4th ed. Basel: Birkhäuser, 1964:148–52.

    Google Scholar 

  34. Fieller EC. A fundamental formula in the statistics of biological assay, and some applications. Quart J Pharm Pharmacol 1944;17:117–23.

    Google Scholar 

  35. Linzenmeier. Cited according to Hallmann L: Klinische Chemie und Mikroskopie. 9th ed. Stuttgart: Thieme, 1960: 358.

  36. Van Eden W, Holoshitz J, Nevo Z, Frenkel A, Klajman A, Cohen IR. Arthritis induced by a T-lymphocyte clone that responds to myobacterium tuberculosis and to cartilage proteoglycans. Proc Natl Acad Sci USA 1985;82:5117–20.

    PubMed  Google Scholar 

  37. Van Eden W, Thole JER, Van der Zee R, Nordzij A, Van Embden JDA, Hensen EJ, et al. Cloning of the mycobacterial epitope recognized by T lymphocytes in adjuvant arthritis. Nature 1988;331:171–3.

    PubMed  Google Scholar 

  38. Zidek Z, Perlik F. Genetic control of adjuvant-induced arthritis in rats. J Pharm Pharmacol 1971;23:389–90.

    PubMed  Google Scholar 

  39. Baumgartner WA, Beck FWJ, Lorber A, Pearson CM, Whitehouse MW. Adjuvant disease in rats: biochemical criteria for distinguishing several phases of inflammation and arthritis. Proc Soc Exp Biol NY 1974;145:625–30.

    Google Scholar 

  40. Muir VY, Dumonde DC. Different strains of rats develop different clinical forms of adjuvant disease. Ann Rheum Dis 1982;41:538–43.

    PubMed  Google Scholar 

  41. Ackermann NR, Rooks WH, Shott L, Genant H, Maloney P, West E. Effects of Naproxen on connective tissue changes in the adjuvant arthritic rats. Arth Rheum 1979;22:1365–74.

    Google Scholar 

  42. Eisen V, Freeman PC, Loverday C, West GB. Blood changes in experimental arthritis in two types of genetically different rats. Br J Pharmacol 1973;49:688–95.

    PubMed  Google Scholar 

  43. Martel RR, Klicins J, Metcalf G, Rona GA. Comparative effects of long term treatment with etodolac, naproxen and ibuprofen on articular and bone changes associated with adjuvant arthritis in rats. Agents Actions 1984;15:403–12.

    PubMed  Google Scholar 

  44. Busch U, Engelhardt G. Distribution of [14C] meloxicam in joints of rats with adjuvant arthritis. Drugs Exptl Clin Res 1990;17:49–52.

    Google Scholar 

  45. Gralla EJ, Wiseman EH. The adjuvant arthritic rat: inflammatory parameters during development and regression of gross lesions. Proc Soc Exp Biol Med 1968;128:493–5.

    PubMed  Google Scholar 

  46. Weichman BN. Rat adjuvant arthritis: A model of chronic inflammation. In: Chang JY, Lewis AJ, editors. Pharmacological methods in the control of inflammation. New York: Alan R. Liss Inc., 1989:363–80

    Google Scholar 

  47. Carlson RP, Datko LJ, O'Neill-Davies L, Blazek EM, De Lustro F, Beideman R, et al. Comparison of inflammatory changes in established Typ II collagen - and adjuvant-induced arthritis using outbred Wistar rats. Int J Immunopharmacol 1985;7:811–26.

    PubMed  Google Scholar 

  48. Lewis AJ, Cottney J, White DD, Fox PK, McNeillie A, Dunlop J, et al. Action of gold salts in some inflammatory and immunological models. Agents Actions 1980;10:63–77.

    PubMed  Google Scholar 

  49. Liyanage SP, Currey HLF. Failure of oral D-penicillamine to modify adjuvant arthritis or immune response in the rat. Ann Rheum Dis 1972;31:521–3.

    PubMed  Google Scholar 

  50. Garrett JP, Whitehouse MW, Vernon-Roberts B, Brooks PM. Ambivalent properties of gold drugs in adjuvant induced polyarthritis in rats. J Rheumatol 1985;12:1079–82.

    PubMed  Google Scholar 

  51. Graeme ML, Fabry E, Sigg EB. Myobacterial adjuvant periarthritis in rodents and its modification by anti-inflammatory agents. J Pharmacol Exp Ther 1966;153:373–80.

    Google Scholar 

  52. Busch U. The pharmacokinetics of meloxicam in animals. Scand J Rheumatol 1994;Suppl 98:A119.

    Google Scholar 

  53. Türk D, Busch U, Heinzel G, Greischel A, Nehmitz G, Narjes H. The basic clinical pharmacokinetics of meloxicam, a new NSAID. Scand J Rheumatol 1994;Suppl 98:A120.

    Google Scholar 

  54. Schmid J, Busch U, Heinzel G, Bozler G, Kaschke S, Kummer M. Meloxicam: pharmacokinetics and metabolic pattern after intravenous infusion and oral administration to healthy subjects. Drug Metab and Dispos 1995. In press.

  55. Smolen JS. New pharmacological disease modifying agents for rheumatoid arthritis. Rheumatol Eur 1995;24(Suppl):194–6.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Engelhardt, G., Homma, D. & Schnitzler, C. Meloxicam: A potent inhibitor of adjuvant arthritis in the Lewis rat. Inflamm Res 44, 548–555 (1995). https://doi.org/10.1007/BF01757360

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01757360

Key words

Navigation