Agents and Actions

, Volume 9, Issue 1, pp 107–116 | Cite as

Comparative effects of drugs on four paw oedema models in the rat

  • David K. Gemmell
  • Jean Cottney
  • Alan J. Lewis
Immunosuppression and Inflammation


The development of novel anti-inflammatory drugs (AID) has been claimed to be dependent on the discovery of models of inflammation that differ from those currently used for drug screening, e.g. carrageenen paw oedema and u.v. erythema. We have thus evaluated the effect of a variety of drugs in a number of novel models of inflammation in the rat produced in the hind paw. We have utilized kaolin, zymosan, anti-rat IgG (anti-IgG) and the Reversed Passive Arthus (RPA) reaction to produce these oedema models.

We found that the non-steroidal AID's, e.g. aspirin, flufenamic acid, indomethacin, naproxen and phenylbutazone, were active in all four tests. Of the nine novel AID examined, levamisole and tetramisole demonstrated considerable activity in all four tests and dapsone was especially active in the anti-IgG and RPA tests. In contrast, the anti-rheumatic d-penicillamine was inactive in all four models. Each of the ten compounds tested which has been claimed to influence complement function, was active in the RPA but not in the kaolin model. These results are discussed in the context of the aetiology of each oedema and the suspected mode of action of the various drugs.


Aspirin Indomethacin Naproxen Kaolin Levamisole 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. [1]
    P. Bresloff,Miscellaneous Antirheumatic Drugs and Their Possible Models of Action, in:Advances in Drug Research, vol. 11 (Academic Press, London, New York and San Francisco, 1977), pp. 1–21.Google Scholar
  2. [2]
    D. A. Willoughby andP. Dieppe,Anti-Inflammatory Models in Animals, in:Future Trends in Inflammation, vol. 11 (Birkhäuser Verlag, Basel and Stuttgart, 1975), pp. 306–312.Google Scholar
  3. [3]
    N. J. Zwaifler,Rheumatoid Synovitis. An Extravascular Immune Complex Disease, Arthritis Rheum.17, 29–305 (1974).Google Scholar
  4. [4]
    A. C. Allison andP. Davies,Mechanisms Underlying Chronic Inflammation, in:Future Trends in Inflammation, vol. 1 (Piccin Books, London, 1974), pp. 449–480.Google Scholar
  5. [5]
    A. W. Ford-Hutchinson, J. R. Walker, N. S. Connor andM. J. H. Smith,Prostaglandins and Leukocyte Migration in Inflammatory Reactions, Agents and Actions7/4, 469–472 (1977).CrossRefGoogle Scholar
  6. [6]
    M. M. Frank, L. Ellman, I. Green andC. G. Cochrane,Site of Deposition of C3 in Arthus Reactions of C4 Deficient Guinea Pigs, J. Immunol.110, 1447–1451 (1973).PubMedGoogle Scholar
  7. [7]
    G. W. Carter andR. A. Krause,The Reversed Passive Arthus Reaction in the Rat: a Potential Screen for Anti-Inflammatory Agents, Fed. Proc.35, 774 (1976).Google Scholar
  8. [8]
    Y.-H. Chang,Mechanism of Action of Colchicine. 1. Effects of Colchicine and Its Analogs on the Reversed Passive Arthus Reaction and the Carrageenan-Induced Hindpaw Oedema in the Rat, J. Pharmacol. Exp. Ther.194, 154–158 (1975).PubMedGoogle Scholar
  9. [9]
    M. B. Goldlust andW. F. Schreiber,Use of the Reversed Passive Arthus Reaction as a Test for Anti-Inflammatory Agents, Agents and Actions5, 39–47 (1975).CrossRefPubMedGoogle Scholar
  10. [10]
    A. Blackham, H. Radziwonik andI. H. Shaw,The Arthus Reaction in Guinea Pig Knee Joints. A Test for Anti-Inflammatory Drugs, Agents and Actions5, 519–527 (1975).CrossRefPubMedGoogle Scholar
  11. [11]
    I. L. Bonta andJ. Noordhoek,Anti-Inflammatory Mechanism of Inflamed Tissue Factor, Agents and Actions3, 348–356 (1973).CrossRefPubMedGoogle Scholar
  12. [12]
    A. J. Lewis,A Comparison of the Anti-Inflammatory Effects of Copper Aspirinate and Other Copper Salts in the Rat and the Guinea Pig, Agents and Actions8, 244–250 (1978).CrossRefPubMedGoogle Scholar
  13. [13]
    A. J. Lewis, J. Cottney andD. J. Nelson,Mechanisms of Phytohaemagglutinin-P, Concanavalin-A and Kaolin-Induced Oedemas in the Rat, Eur. J. Pharmac.40, 1–8 (1976).CrossRefGoogle Scholar
  14. [14]
    J. Noordhoek, M. R. Nagy andI. L. Bonta,Involvement of Complement and Kinins in Some Non-Immunogenic Paw Inflammations in Rats, in:I. L. Bonta,Recent Developments in the Pharmacology of Inflammatory Mediators (Birkhäuser Verlag, Basel and Stuttgart, 1977), pp. 109–121.Google Scholar
  15. [15]
    P. S. Ringrose, M. A. Parr andM. McLaren,Effects of Anti-Inflammatory and Other Compounds on the Release of Lysosomal Enzymes from Macrophages, Biochem. Pharmac.24, 607–614 (1975).CrossRefGoogle Scholar
  16. [16]
    E. C. Keystone, C. P. Schorlemmer, C. Pope andA. C. Allison,Zymosan-Induced Arthritis. A Model of Chronic Proliferative Arthritis Following Activation of the Alternative Pathway of Complement, Arth. Rheum.20, 1396–1401 (1977).Google Scholar
  17. [17]
    M. B. Goldlust, T. W. Harrity andD. M. Palmer,Evaluation of Anti-rheumatic drugs Using the Cutaneous Arthus Reaction, in:D. C. Dumonde andM. K. Jasani,The Recognition of Anti-Rheumatic Drugs (M.T.P. Press Ltd., Lancaster, 1978), pp. 119–136.Google Scholar
  18. [18]
    G. Ungar, S. Kobrin andB. R. Sezeny,Measurement of Inflammation and Evaluation of Anti-Inflammatory Agents, Arch. Int. Pharmacodyn.123, 71–77 (1959).PubMedGoogle Scholar
  19. [19]
    K. F. Austen andE. L. Becker,Mechanisms of Immunologic Injury of Rat Peritoneal Mast Cells. II. Complement Requirement and Phosphonate Ester Inhibition of Release of Histamine by Rabbit Anti-Rat Gamma Globulin, J. Exp. Med.124, 397–416 (1966).CrossRefPubMedGoogle Scholar
  20. [20]
    C. G. Cochrane,The Arthus and Related Reactions, inC. A. Williams andM. W. Chase,Methods in Immunology and Immunochemistry, vol. V,Antigenantibody Reactions in Vivo (Academic Press, Inc., New York, San Francisco, London, 1976), pp. 159–175.Google Scholar
  21. [21]
    K. Whaley, D. J. P. Sloane, A. G. Davidson andP. M. Brooks,Studies of the Action of Some Anti-Inflammatory Drugs on Complement Mediated Immune Haemolysis, Br. J. clin. Pharmac.2, 123–129 (1975).Google Scholar
  22. [22]
    J. R. Vane,Inhibition of Prostaglandin Synthesis as a Mechanism of Action for Aspirin-Like Drugs, Nature New Biol.231 232–235 (1971).PubMedGoogle Scholar
  23. [23]
    D. C. Atkinson, K. E. Godfrey, B. J. Jordan, E. C. Leach B. E. Meek, J. D. Nichols andJ. F. Saville,2-(2,4-Dichlorophenoxy) Phenylacetic Acid (Fenclofenac): One of a Novel Series of Anti-Inflammatory Compounds with Low Ulcerogenic Potential, J. Pharm. Pharmacol.26, 357–359 (1974).PubMedGoogle Scholar
  24. [24]
    F. M. Andrews, D. N. Golding, A. M. Freeman, J. R. Golding, A. T. Day, A. G. S. Hill, A. V. Camp, E. Lewis-Fanning andW. H. Lyle,Controlled Trial of D-Penicillamine in Severe Rheumatoid Arthritis, Lancet1, 275–280 (1973).PubMedGoogle Scholar
  25. [25]
    R. Lisciani, P. Scorza Barcellona andB. Silvestrini,Researches on the Topical Activity of Benzydamine, European J. Pharmacol.3, 157–162 (1978).CrossRefGoogle Scholar
  26. [26]
    L. M. Lichtenstein andN. F. Adkinson,Chlorphenesin: a New Inhibitor of IgE Mediated Histamine Release, J. Immunol.103, 866–868 (1969).PubMedGoogle Scholar
  27. [27]
    Y.-H. Chang,Mechanism of Action of Colchicine. II. Effects of Colchicine and Its Analogs on Phagocytosis and Chemotaxis in Vitro, J. Pharmacol. Exp. Ther.194, 159–164 (1975).PubMedGoogle Scholar
  28. [28]
    D. M. Thompson andD. Souhami,Suppression of the Arthus Reaction in the Guinea Pig by Dapsone, Proc. Roy. Soc. Med.68, 273 (1975).PubMedGoogle Scholar
  29. [29]
    S. I. Katz, K. C. Hertz, P. S. Crawford, L. A. Gazze, M. M. Frank andT. J. Lawley,Effect of Sulphones on Complement Deposition in Dermatitis Herpetiformis and on Complement-Mediated Guinea Pig Reactions, J. Invest. Derm.67, 688–690 (1976).CrossRefPubMedGoogle Scholar
  30. [30]
    B. McConkey, P. Davies, R. A. Crockson, A. P. Crockson, M. Butler andT. J. Constable,Dapsone in Rheumatoid Arthritis, Rheum. Rehabil.15, 230–234 (1976).Google Scholar
  31. [31]
    A. J. Lewis, D. K. Gemmell andW. H. Stimson,The Anti-Inflammatory Profile of Dapsone in Animal Models of Inflammation, Agents Actions.8, 578–586 (1978).CrossRefPubMedGoogle Scholar
  32. [32]
    J. Symoens andM. Rosenthal,Levamisole in the Modulation of the Immune Response: the Current Experimental and Clinical State, J. Reticuloendothel. Soc.21, 175–221 (1977).PubMedGoogle Scholar
  33. [33]
    T.-S. Yeoh, E.-H. Yap, M. Singh andB.-C. Ho,Drug Inhibition of Anaphylactic Histamine Release from Peritoneal Cells of Rats Infected with Toxocara canis, Int. Archs. Allergy appl. Immunol.49, 371–380 (1975).Google Scholar
  34. [34]
    T. di Perri, F. Auteri, F. L. Pasani andF. Mattioli,Biological, Chemical and Pharmacological Induction of the Properdin-Mediated Pathway of Complement Activation in Vitro, in:D. A. Willoughby,J. P. Giroud andG. P. Velo,Perspectives in Inflammation. Future Trends and Developments (M.T.P. Press Ltd., Lancaster, 1977), pp. 405–416.Google Scholar
  35. [35]
    J. S. C. Fong andR. A. Good,Suramin — a Potent Reversible and Competitive Inhibitor of Complement Systems, Clin. Exp. Immunol.10, 127–138 (1972).PubMedGoogle Scholar
  36. [36]
    V. Eisen andC. Loveday,Effects of Suramin on Complement, Blood Clotting, Fibrinolysis and Kinin Formation, Br. J. Pharmac.49, 678–687 (1973).Google Scholar
  37. [37]
    N. A. Soter, K. F. Austen andI. Gigli,Inhibition by ɛ-Amino Caproic Acid of the Activation of the First Component of the Complement System, J. Immunol.114, 928–932 (1975).PubMedGoogle Scholar
  38. [38]
    F. B. Taylor, andH. Fudenberg,Inhibition of the C 1 Component of Complement by Amino Acids, Immunology7, 319–331 (1964).Google Scholar
  39. [39]
    T. di Perri andA. Auteri,Anticomplementary Properties of Cinnarizine, Arch. int. Pharmacodyn.203, 23–29 (1973).PubMedGoogle Scholar

Copyright information

© Birkhäuser-Verlag 1979

Authors and Affiliations

  • David K. Gemmell
    • 1
  • Jean Cottney
    • 1
  • Alan J. Lewis
    • 1
  1. 1.Scientific Development GroupOrganon Laboratories LimitedNewhouseScotland

Personalised recommendations