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Adjuvant Arthritis in the Rat

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

1Institute of Infectious Diseases and Immunology, Utrecht, The Netherlands, 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

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

Basic Protocol: Induction of Adjuvant Arthritis

 Materials
  • 10 mg/ml heat-killed Mycobacterium tuberculosis (strain H37Ra) suspended in incomplete Freund's adjuvant (IFA; see Support Protocol)
  • 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: 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.

Looking for materials?  Suppliers Guide
     
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Figures

  • Figure 15.4.1
    Time line for key events in the development of adjuvant arthritis (AA). Mt, injection of Mycobacterium tuberculosis; LST, lymphocyte stimulation test, a proliferative assay of T cell response.

    View Image
  • Figure 15.4.2
    Mean body weights of rats during the active phase of adjuvant arthritis (AA). Body weights of five 8-week-old Lewis rats immunized at day 0 for induction of adjuvant arthritis with 6 mg/ml Mycobacterium tuberculosis H37Ra in mineral oil (arthritis rats) are shown. Clinical arthritis was seen to develop from day 13 onwards. Mean body weights of nonimmunized animals of the same age (normal rats) are shown as a control. An immediate decline in weight development is seen at the time of arthritis development. At the time of AA remission (day 30) weight is increasing again.

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Literature Cited

Literature Cited
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    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.
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