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Adjuvant polyarthritis in rats: is this a satisfactory model for screening anti-arthritic drugs?

  • Immunosuppression and Inflammation
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Summary

The pathological and biochemical features of the polyarthritis in rats induced by Freund's adjuvant are briefly reviewed. The object of this is to highlight recent studies that provide a basis for specifically improving procedures employed in screening the activity and mode of action of anti-inflammatory/antiarthritic drugs-especially those with possible disease modifying activity.

Current screening procedures involve the simple measurement of hind-paw or joint swelling. This may not reflect the extent of degradation or systemic changes in arthritis. It is suggested that it is possible to more precisely measure the extent of joint degradation by the following:

  1. (1)

    X-ray monitoring of joints afflicted with the disease,

  2. (2)

    Histological and morphological examination (the latter in alkali cleared — Alizarin stained preparations) of hindlimbs,

  3. (3)

    Quantitative histoenzymic and biochemical analysis of degradative enzymes and inflammatory mediators.

Additional to this specific immunological and systemic (blood, liver) changes should be measured in primary screening in recognition that arthritis is a disease not only of joints but involving the immune, hepatic and possibly other organ systems and that these systemic components clearly have effects on joints.

Only by a combined analysis of both local joint and systemic changes during drug treatment will it be possible to discriminate new drugs with disease-modifying activity.

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References

  1. C.M. Pearson, InArthritis and Allied Conditions, pp. 119–129. (Ed.J.L. Hollander). Henry Kimpton, London 1966.

    Google Scholar 

  2. K.F. Swingle. InAnti-Inflammatory Drugs. Chemistry and Pharmacology, vol. 2, pp. 33–122. (EdsR.A. Scherrer andM.W. Whitehouse). Academic Press, New York 1974.

    Google Scholar 

  3. A.S. Watnick. InImmunopharmacology, pp. 155–171. (EdsM.E. Rosenthale andH. Mansmann). Spectrum, New York 1975.

    Google Scholar 

  4. C.G. Van Arman, Fedn. Proc.35, 2442–2446 (1976).

    Google Scholar 

  5. W.C. Dick.An Introduction to Clinical Rheumatology. Churchill-Livingstone, Edinburgh 1972.

    Google Scholar 

  6. E. Fujihira, T. Mori andM. Nakazawa, Pharmacometrics4, 897–902.

  7. A.A. Amkraut, G.F. Solomon andH. Kramer. Psychosomatic Med.33, 203–214 (1971).

    Google Scholar 

  8. F.W.J. Beck andM.W. Whitehouse, Proc. Soc. Exp. Biol. Med.146, 665–669 (1974).

    PubMed  Google Scholar 

  9. M.W. Whitehouse andF.W.J. Beck, Agents and Actions4, 227–229 (1974).

    Google Scholar 

  10. M.W. Whitehouse et al., Immunology27, 311–329 (1974).

    PubMed  Google Scholar 

  11. S.P. Liyanage, H.L.F. Currey andB. Vernon-Roberts, Ann. Rheum. Dis.34, 49–53 (1975).

    PubMed  Google Scholar 

  12. H. Metzke, Ddr. Allerg. Immunol. Leipzig.23, 206–210 (1976).

    Google Scholar 

  13. W. Mohr andA. Wild, Arzneim.-Forsch.26, 1860–1866 (1976).

    Google Scholar 

  14. M.W. Whitehouse. InImmunochemistry: Advanced Textbook, pp. 571–601. (EdsL.E. Glynn andM.W. Stewart). Wiley, Chichester, UK 1977.

    Google Scholar 

  15. B. Vernon-Roberts, S.P. Liyanage andH.L.F. Currey. Ann. Rheum. Dis.35, 389–397 (1976).

    Google Scholar 

  16. B.H. Waksman, T.M. Pearson andJ.T. Sharp, J. Immunol.85, 403–417 (1960).

    PubMed  Google Scholar 

  17. B.B. Newbold, Br. J. Exp. Path.45, 375–383 (1964).

    Google Scholar 

  18. B.B. Newbold, Ann. Rheum. Dis.23, 392–396 (1964).

    Google Scholar 

  19. C.M. Pearson andF.D. Wood, J. Exp. Med.120, 547–560 (1964).

    Google Scholar 

  20. D.J. Whitehouse, M.W. Whitehouse andC.M. Pearson, Nature224, 1322 (1969).

    PubMed  Google Scholar 

  21. T. Koga andC.M. Pearson, J. Immunol.111, 599–608 (1973).

    PubMed  Google Scholar 

  22. T. Koga et al., Int. Archs. Allergy Appl. Immunol.51, 206–213

  23. T. Koga et al., Int. Archs. Allergy Appl. Immunol.51, 359–367

  24. E.M. Glenn andJ. Gray, Am. J. Vet. Res.26, 1180–1194 (1965).

    PubMed  Google Scholar 

  25. T. Koga, A. Tanaka andC.M. Pearson, Int. Archs. Allergy Appl. Immunol.51, 583–593 (1976).

    Google Scholar 

  26. Y.H. Chang, C.M. Pearson andL. Chedid, J. Exp. Med.153, 1021–1026 (1981).

    Article  PubMed  Google Scholar 

  27. L. Kourounakis andM.A. Kapusta, J. Rheumatol.3, 346–354 (1976).

    PubMed  Google Scholar 

  28. Y.H. Chang, J. Pharm. Exp. Therap.201, 1–7 (1977).

    Google Scholar 

  29. H. Kayashima, T. Koga andK. Onoue, J. Immunol.120, 1127–1131.

  30. K.R. Gans, S. Heyner andR.F. Orzechowski, Arth. Rheum.23, 633–640 (1980).

    Google Scholar 

  31. E.D. Harris. InTextbook of Rheumatology, pp. 896–927. (EdsW.N. Kelley et al.) 1981.

  32. Y.H. Chang, C.M. Pearson andC. Abe, Arth. Rheum.23, 62–71 (1980).

    Google Scholar 

  33. Y.H. Chang, J. Pharmacol. Exp. Ther.203, 156–161 (1977).

    PubMed  Google Scholar 

  34. Y.H. Chang andW. Hoffman, Arth. Rheum.20, 1507–1513 (1977).

    Google Scholar 

  35. M.A. Kapusta andJ. Mendelson, Arth. Rheum.10, 288 (1967).

    Google Scholar 

  36. M. Evinger, S. Maeda andS. Pesta, J. Biol. Chem.256, 2113–2114 (1981).

    PubMed  Google Scholar 

  37. C.M. Pearson andF.D. Wood, Am. J. Pathol.42, 73–95 (1963).

    PubMed  Google Scholar 

  38. E.M. Glenn andJ. Gray, Am. J. Vet. Res.26, 1180–1194 (1965).

    PubMed  Google Scholar 

  39. K.D. Muirden andG. Peace, Ann. Rheum. Dis.28, 392–401 (1969).

    PubMed  Google Scholar 

  40. T. Mori, Y. Tsubura, E. Fujhira, S. Otoma andM. Nakazawa, Pharmacometrics4, 1051–1062 (1970).

    Google Scholar 

  41. R.B. Zurier andM. Ballas, Arth. Rheum.16, 251–258 (1973).

    Google Scholar 

  42. K. Militzer, Arzneim.-Forsch.25, 1884–1889 (1975).

    Google Scholar 

  43. F.R. Nusbickel andH. Troyer, Arth. Rheum.19, 1339–1346 (1976).

    Google Scholar 

  44. W. Mohr andA. Wild, Wien. Klin. Wochenschr.89, 756–765 (1977).

    PubMed  Google Scholar 

  45. H.G. Fassbender. InChronic Forms of Polyarthritis, pp. 17–26. (Ed.F.J. Wagenhaeuser). Hans Huber, Berne 1976.

    Google Scholar 

  46. M.J. Parnham, J. Pathol.132, 11–21 (1980).

    Article  PubMed  Google Scholar 

  47. E.M. Glenn, J. Gray andW. Kooyers, Am. J. Vet. Res.26, 1195–1203 (1965).

    PubMed  Google Scholar 

  48. P. Görög andB. Kovaks, Agents and Actions6, 607–612 (1976).

    PubMed  Google Scholar 

  49. S.J. Piliero andC. Colombo, J. Pharm. Exp. Ther.165, 294–299 (1969).

    Google Scholar 

  50. A.J. Collins andD.A. Lewis, Biochem. Pharmac.20, 251–253 (1971).

    Article  Google Scholar 

  51. D.T. Waltz, M.J. Di Martino, J.H. Kuch andW. Zuccarello, Proc. Soc. Exp. Biol. Med.136, 907–910 (1971).

    PubMed  Google Scholar 

  52. M. Sternberg, J. Peyroux, A. Grochulski et al., Can. J. Physiol. Pharmacol.53, 368–374 (1975).

    PubMed  Google Scholar 

  53. D.P. Parrott andD.A. Lewis, Ann. Rheum. Dis.36, 166–169 (1977).

    PubMed  Google Scholar 

  54. P.J. Rooney, W.C. Dick, R.C. Imrie et al., Ann. Rheum. Dis.37, 432–435 (1978).

    PubMed  Google Scholar 

  55. E.M. Glenn, B.J. Bowman, N.A. Rohloff andR.J. Seely, Agents and Actions7, 265–282 (1977).

    PubMed  Google Scholar 

  56. T. Kuberasampath andS.M. Bose, Agents and Actions10, 78–84 (1980).

    PubMed  Google Scholar 

  57. E. Fujihira, T. Mori andM. Nakazawa, Pharmacometrics4, 903–910 (1970).

    Google Scholar 

  58. L. Kourounakis andM.A. Kapusta, Ann. Rheum. Dis.33, 185–189 (1974).

    PubMed  Google Scholar 

  59. A. Kahan, F. Perlik, A. Le Go, F. Delbarre andJ.P. Giroud. InFuture Trends in Inflammation II, pp. 219–226. (EdsJ.P. Giroud, D.A. Willoughby andG.P. Velo). Birkhäuser, Basel 1975.

    Google Scholar 

  60. L. Binderup, E. Bramm andE. Arrigoni-Martelli, Experientia33, 390–391 (1976).

    Google Scholar 

  61. D.M. Morton andD.H. Chatfield, Biochem. Pharmac.19, 473–481.

  62. M.W. Whitehouse andF.J. Beck, Drug Metab. Distrib.1, 251–255 (1973).

    Google Scholar 

  63. P.P. Mathur, R.D. Smyth, C.M. Witmer andG.S. Carr, Biochem. Pharmac.27, 1771–1774 (1978).

    Article  Google Scholar 

  64. E. Arrigoni-Martelli andA. Restelli, Eur. J. Pharmacop.19, 191–198 (1972).

    Article  Google Scholar 

  65. G.J. Barritt andM.W. Whitehouse, Biochem. Med.17, 99–115 (1977).

    Article  PubMed  Google Scholar 

  66. A.J. Anderson, Ann. Rheum. Dis.29, 307–313 (1970).

    PubMed  Google Scholar 

  67. M.J. Parnham, I.L. Bonta andM.J.P. Adolfs, Ann. Rheum. Dis.37, 218–224 (1978).

    PubMed  Google Scholar 

  68. B. Exer, P. Krupp, R. Menasse andL. Riesterer, Agents and Actions6, 651–656 (1976).

    PubMed  Google Scholar 

  69. N.R. Ackerman, W.H. Rooks II, L. Schott, H. Genant, P. Mahoney andE. West, Arth. Rheum.22, 1365–1374 (1979).

    Google Scholar 

  70. D.N. Bensley andR. Nickander, Eur. J. Rheumatol. Inflam.2, 175–185 (1982).

    Article  Google Scholar 

  71. S. Wong, J.F. Gardocki andT.P. Pruss, J. Pharmacol. Exp. Ther.185, 127–138 (1973).

    PubMed  Google Scholar 

  72. A.D. Pearse, Histochem. J.6, 431–446 (1974).

    Article  PubMed  Google Scholar 

  73. F.R. Nusbickel andW. Johnson,Histochem.J. 11, 587–598 (1979).

    Article  PubMed  Google Scholar 

  74. F.R. Nusbickel,Histochem. J. 11, 573–585 (1979).

    Article  PubMed  Google Scholar 

  75. L. Szanto, D. Tanka andM. Kellner, Int. J. Clin. Pharmacol.13, 113–119 (1976).

    Google Scholar 

  76. J. Lunec, S.P. Halloran, A.G. White andT.L. Dormandy, J. Rheumatol.8, 233–245 (1981).

    PubMed  Google Scholar 

  77. Z. Trnavska andK. Trnavsky, Pharmacology12, 110–116 (1974).

    PubMed  Google Scholar 

  78. L. Kourounkis andM.A. Kapusta, J. Rheumatol.3, 346–354 (1976).

    PubMed  Google Scholar 

  79. H. Tannenbaum andK. Poskitt, J. Rheumatol.7, 801–806 (1980).

    PubMed  Google Scholar 

  80. K.R. Gaus, S. Heyner andR.F. Orzechowski, Arth. Rheum.23, 633–640 (1980).

    Google Scholar 

  81. C.N. Rao, V.H. Rao, L. Verbruggen andS. Orloff, Scand. J. Rheumatol.9, 280–284 (1980).

    PubMed  Google Scholar 

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This is dedicated to the late Carl Pearson, who did so much to foster studies on the adjuvant arthritic rat as a model for human arthritic conditions and in his recent untimely death will be recognized as a pioneer who will be sadly missed.

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Rainsford, K.D. Adjuvant polyarthritis in rats: is this a satisfactory model for screening anti-arthritic drugs?. Agents and Actions 12, 452–458 (1982). https://doi.org/10.1007/BF01965926

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