Adjuvant Arthritis in the Rat

Willem van Eden1, Josee P.A. Wagenaar‐Hilbers1, Marca H.M. Wauben1

1 Institute of Infectious Diseases and Immunology, Utrecht, The Netherlands
Publication Name:  Current Protocols in Immunology
Unit Number:  Unit 15.4
DOI:  10.1002/0471142735.im1504s19
Online Posting Date:  May, 2001
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Abstract

Adjuvant arthritis (AA) is an induced form of (sub)chronic arthritis. Strains of rats have a varying genetic susceptibility to AA, whereas mice generally are not susceptible. AA is most easily induced with mycobacteria suspended in oil, although in some strains of rats it can be induced with oily adjuvants in the absence of mycobacteria. The disease is a T cell‐mediated autoimmune arthritis that is frequently used to study immunological aspects of rheumatoid arthritis (RA) and other arthritic or inflammatory diseases in humans. Furthermore, it is used as a model for developing and testing antiinflammatory drugs. There are no particularly well‐defined autoantigens in AA; in this respect, the model resembles spontaneous arthritic diseases in humans. In all susceptible rat strains, the inflammatory process of AA is self remitting, although usually the disease is severe and leads to permanent joint malformations, including ankylosis; a time line for AA development is presented. This unit describes the induction and evaluation of AA and the preparation of adjuvant used to induce AA.

     
 
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Table of Contents

  • Basic Protocol 1: Induction of Adjuvant Arthritis
  • Support Protocol 1: Preparation of Mycobacteria Suspension
  • Commentary
  • Literature Cited
  • Figures
  • Tables
     
 
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Materials

Basic Protocol 1: Induction of Adjuvant Arthritis

  Materials
  • 10 mg/ml heat‐killed Mycobacterium tuberculosis (strain H37Ra) suspended in incomplete Freund's adjuvant (IFA; see protocol 2)
  • Lewis rats, 6 to 12 weeks old and pathogen free
  • 1‐ml glass syringe
  • 20‐ and 25‐G needles
  • Scale
  • Restraining device for rats
  • Wet cotton
  • Additional reagents and equipment for animal care, handling, and restraint (units 1.1 1.5)

Support Protocol 1: Preparation of Mycobacteria Suspension

  Materials
  • 100 mg dried, heat‐killed Mycobacterium tuberculosis (strain H37Ra)
  • 10 ml incomplete Freund's adjuvant (IFA; Difco)
  • Pestle and ∼7‐cm‐diameter roughened glass or porcelain mortar
  • 15‐ml plastic or glass tube
CAUTION: Wear gloves when handling the suspension of mycobacteria in oil, as it may be irritating and potentially sensitizing for humans.
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Figures

Videos

Literature Cited

Literature Cited
   Anderton, S.M., Van der Zee, R., Prakken, B., Noordzij, A., and van Eden, W. 1995. Activation of T cells recognizing self 60‐kDa heat shock protein can protect against experimental arthritis. J. Exp. Med. 181:943‐952.
   Battisto, J.R., Smith, R.N., Beckman, K., Sternlicht, M., and Welles, W.L. 1982. Susceptibility to adjuvant arthritis in DA and F344 rats. Arthritis Rheum. 25:1194‐1199.
   Bersani‐Amado, C.A., Duarte, A.J., Tanji, M.M., Cianga, M., and Jancar, S. 1990. Comparative study of adjuvant‐induced arthritis in susceptible and resistant strains of rats. III. Analysis of lymphocyte subpopulations. J. Rheumatol. 17:153‐158.
   Best, R., Christian, R., and Lewis, D.A. 1984. Effect of particle size of dried mycobacteria on adjuvant‐induced arthritis in the rat. Agents Actions 14:265‐268.
   Billingham, M.E.J., Carney, S., Butler, R., and Colston, J. 1990. A mycobacterial 65‐kDa heat shock protein induces antigen‐specific suppression of adjuvant arthritis, but is not itself arthritogenic. J. Exp. Med. 171:339‐344.
   Cozine, W.S., Stanfield, A.B., Staephens, C.A.L., and Mazur, M.T. 1972. Adjuvant disease—The paradox of prevention and induction with complete Freund's adjuvant. Proc. Soc. Exp. Biol. 141:911‐914.
   Glenn, E.M. and Gray, J. 1965. Adjuvant‐induced polyarthritis in rats: Biologic and histologic background. Am. J. Vet. Res. 26:1180‐1194.
   Griffiths, M.M. 1988. Immunogenetics of collagen‐induced arthritis in rats. Int. Rev. Immunol. 4:1‐15.
   Harris, J.M. and Spencer, A. 1962. A modified plethysmographic apparatus for recording volume changes in the rat paw. J. Pharm. Pharmacol. 14:464‐466.
   Holoshitz, J., Naparstek, Y., Ben‐Nun, A., and Cohen, I.R. 1983. Lines of T lymphocytes induce or vaccinate against autoimmune arthritis. Science 219:56‐58.
   Kayashima, K., Koga, T., and Onoue, K. 1976. Role of T lymphocytes in adjuvant arthritis. Evidence for the regulatory function of thymus‐derived cells in the induction of the disease. J. Immunol. 117:1878‐1883.
   Kleinau, S., Erlandsson, H., Holmdahl, R., and Klareskog, L. 1991. Adjuvant oils induce arthritis in the DA rat. I. Characterization of the disease and evidence for an immunological involvement. J. Autoimmun. 4:871‐880.
   Koga, T., Kato, K., Kotani, S., Tanaka, A., and Pearson, C.M. 1976. Effect of degradation of the arabinomannan portion of a water‐soluble component of M. tuberculosis Wax D on polyarthritis induction in the rat. Int. Arch. Allergy Appl. immunol. 51:395‐400.
   Koga, T. and Pearson, C. 1973. Immunogenicity and arthritogenicity in the rat of an antigen from Mycobacterium tuberculosis Wax D. J. Immunol. 111:599‐608.
   Kohashi, O., Kuwata, J., Umehara, K., Uemura, F., Takahasi, T., and Ozawa, A. 1979. Susceptibility to adjuvant arthritis among germ‐free, specific pathogen–free, and conventional rats. Infect. Immun. 26:791‐794.
   Larsson, P., Holmdahl, R., Dencker, L., and Klareskog, L. 1985. In vivo treatment with w3/13 (anti‐pan‐T) but not with OX8 (anti‐suppressor/cytotoxic T) monoclonal antibodies impedes the development of adjuvant arthritis in rats. Immunology 56:383‐391.
   Parrott, D.P. and Lewis, D.A. 1977. Protease and antiprotease levels in blood of arthritic rats. Ann. Rheum. Dis. 36:166‐169.
   Pearson, C.M. 1956. Development of arthritis, periarthritis and periostitis in rats given adjuvant. Proc. Soc. Exp. Biol. Med. 112:95‐101.
   Pearson, C.M., Waksman, B.H., and Sharp, J.T. 1961. Studies of arthritis and other lesions induced in rats by injection of mycobacterial adjuvant. J. Exp. Med. 113:485‐510.
   Rosenthale, M.E. 1970. A comparative study of the Lewis and Sprague Dawly rat in adjuvant arthritis. Arch. Int. Pharmacodyn. 188:14‐22.
   Snippe, H. and Kraaieveld, C.H. 1989. The immunoadjuvant dimethyldioctadecyl‐ammonium bromide. In Immunological Adjuvants and Vaccines (G. Gregoriades, A.C. Allison, and G. Poste, eds.) pp. 47‐50. Plenum Press, New York.
   Stanescu, R., Lider, O., van Eden, W., Holoshitz, J., and Cohen, I.R. 1987. Histopathology of arthritis induced in rats by active immunization to mycobacterial antigens or by systemic transfer of T lymphocyte line. Arthritis Rheum. 30:779‐792.
   Swingle, K.F., Jaques, L.W., and Kram, D.C. 1969. Differences in the severity of adjuvant arthritis in four strains of rats. Proc. Soc. Exp. Biol. Med. 132:608‐612.
   Taurog, J.D., Sandberg, G.P., and Mahowald, M.L. 1983. The cellular basis of adjuvant arthritis. II. Characterization of the cells mediating passive transfer. Cell Immunol. 80:193‐204.
   Taurog, J.D., Kerwar, S.S., McReynolds, R.A., Sanberg, G.P., Leary, S.L., and Mahowald, M.L. 1985. Synergy between adjuvant arthritis and collagen‐induced arthritis in rats. J. Exp. Med. 162:962‐978.
   Terrier, F., Hricak, H.L., Revel, D., Alpers, C.E., Reinold, C.E., Levine, J., and Genant, H.K. 1985. Magnetic resonance imaging and spectroscopy of the periarticular inflammatory soft‐tissue changes in experimental arthritis of the rat. Invest. Radiol. 20:813‐823.
   Torisu, M., Miyahara, T., Shinohara, N., Ohsato, K., and Sonazaki, H. 1978. A new side effect of BCG immunotherapy—BCG‐induced arthritis in man. Cancer Immunol. Immunother. 5:77‐83.
   Trentham, D.E., Townes, A.S., and Kang, A.H. 1977. Autoimmunity to type II collagen: An experimental model of arthritis. J. Exp. Med 146:857‐868.
   van Eden, W., Holoshitz, J., Nevo, Z., Frenkel, A., Klajman, A., and Cohen, I.R. 1985. Arthritis induced by a T‐lymphocyte clone that responds to M. tuberculosis and to cartilage proteoglycans. Proc. Natl. Acad. Sci. U.S.A. 82:5117‐5120.
   van Eden, W., Thole, J.E.R., Van der Zee, R., Noordzij, A., Van Embden, J.D.A., Hensen, E.J., and Cohen, I.R. 1988. Cloning of the mycobacterial epitope recognized by T lymphocytes in adjuvant arthritis. Nature 331:171‐173.
   van Vollenhoven, R.F., Soriano, A., McCarthy, P.E., Schwartz, R.L., Garbrecht, F.C., Thorbecke, G.J., and Siskind, G.W. 1988. The role of immunity to cartilage proteoglycan in adjuvant arthritis: Intravenous injection of bovine proteoglycan enhances adjuvant arthritis. J. Immunol. 141:1168‐1173.
   Vingsbo, C., Jonsson, R., and Holmdahl, R. 1985. Avridine‐induced arthritis in rats: A T cell–dependent chronic disease influenced both by MHC genes and by non‐MHC genes. Clin. Exp. Immunol. 99:359‐363.
   Whitehouse, M.W., Orr, K.J., Beek, W.J., and Pearson, C.M. 1974. Freund's adjuvants: Relationship to arthritogenicity and adjuvanticity in rats to vehicle composition. Immunology 27:311‐330.
   Yiagou, M. and Hadjipetrou‐Kourounakis, L. 1983. Effect of diet on adjuvant‐induced disease and mitogenic responses of Fisher rats. Int. Arch. Allergy Appl. immunol. 71:373‐376.
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