Logo of amjpatholAmerican Journal of Pathology For AuthorsAmerican Journal of Pathology SubscribeAmerican Journal of Pathology SearchAmerican Journal of Pathology Current IssueAmerican Journal of Pathology About the JournalAmerican Journal of Pathology
Am J Pathol. Nov 1996; 149(5): 1675–1683.
PMCID: PMC1865278

Pristane-induced arthritis in rats: a new model for rheumatoid arthritis with a chronic disease course influenced by both major histocompatibility complex and non-major histocompatibility complex genes.


We present a novel animal model for rheumatoid arthritis induced with a well defined synthetic adjuvant oil, pristane. Two weeks after a single intradermal injection of 150 microliters of pristane, the rats developed severe and chronic arthritis. The inflammation was restricted to the joints and involved pannus formation, major histocompatibility complex (MHC) class II expression, and T lymphocyte infiltration. The initial development as well as the chronic stage of pristane-induced arthritis was ameliorated by treatment with antibodies to the alpha beta-T-cell receptor showing that the disease is T cell dependent. Increased levels of interleukin in serum was seen after pristane injection but not during the chronic stage of arthritis. Joint erosions were accompanied by elevated serum levels of cartilage oligomeric matrix protein. Comparison of MHC congenic LEW strains showed that the severity and chronicity of arthritis varied among the different MHC haplotypes. Rats with RT1f haplotype showed a significantly higher susceptibility to pristane-induced arthritis. A strong influence of non-MHC genes was also suggested by the variability of arthritis susceptibility among different strains with the same MHC haplotype; the most susceptible background was the DA and the least susceptible was the E3. Arthritis induced with a well defined nonimmunogenic adjuvant, with a disease course that closely resembles that of rheumatoid arthritis, makes a suitable animal model for future studies of the pathology and genetics of rheumatoid arthritis.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.7M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • PEARSON CM. Development of arthritis, periarthritis and periostitis in rats given adjuvants. Proc Soc Exp Biol Med. 1956 Jan;91(1):95–101. [PubMed]
  • Holmdahl R, Kvick C. Vaccination and genetic experiments demonstrate that adjuvant-oil-induced arthritis and homologous type II collagen-induced arthritis in the same rat strain are different diseases. Clin Exp Immunol. 1992 Apr;88(1):96–100. [PMC free article] [PubMed]
  • Holmdahl R, Goldschmidt TJ, Kleinau S, Kvick C, Jonsson R. Arthritis induced in rats with adjuvant oil is a genetically restricted, alpha beta T-cell dependent autoimmune disease. Immunology. 1992 Jun;76(2):197–202. [PMC free article] [PubMed]
  • Chang YH, Pearson CM, Abe C. Adjuvant polyarthritis. IV. Induction by a synthetic adjuvant: immunologic, histopathologic, and other studies. Arthritis Rheum. 1980 Jan;23(1):62–71. [PubMed]
  • Vingsbo C, Jonsson R, Holmdahl R. Avridine-induced arthritis in rats; a T cell-dependent chronic disease influenced both by MHC genes and by non-MHC genes. Clin Exp Immunol. 1995 Mar;99(3):359–363. [PMC free article] [PubMed]
  • Holmdahl R, Vingsbo C, Mo JA, Michaëlsson E, Malmström V, Jansson L, Brunsberg U. Chronicity of tissue-specific experimental autoimmune disease: a role for B cells? Immunol Rev. 1995 Apr;144:109–135. [PubMed]
  • Whitehouse MW, Orr KJ, Beck FW, Pearson CM. Freund's adjuvants: relationship of arthritogenicity and adjuvanticity in rats to vehicle composition. Immunology. 1974 Aug;27(2):311–330. [PMC free article] [PubMed]
  • Potter M, Wax JS. Genetics of susceptibility to pristane-induced plasmacytomas in BALB/cAn: reduced susceptibility in BALB/cJ with a brief description of pristane-induced arthritis. J Immunol. 1981 Oct;127(4):1591–1595. [PubMed]
  • Bedwell AE, Elson CJ, Hinton CE. Immunological involvement in the pathogenesis of pristane-induced arthritis. Scand J Immunol. 1987 Apr;25(4):393–398. [PubMed]
  • Wooley PH, Seibold JR, Whalen JD, Chapdelaine JM. Pristane-induced arthritis. The immunologic and genetic features of an experimental murine model of autoimmune disease. Arthritis Rheum. 1989 Aug;32(8):1022–1030. [PubMed]
  • Jonsson R, Tarkowski A, Klareskog L. A demineralization procedure for immunohistopathological use. EDTA treatment preserves lymphoid cell surface antigens. J Immunol Methods. 1986 Apr 3;88(1):109–114. [PubMed]
  • Hsu SM, Raine L, Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. [PubMed]
  • Hünig T, Wallny HJ, Hartley JK, Lawetzky A, Tiefenthaler G. A monoclonal antibody to a constant determinant of the rat T cell antigen receptor that induces T cell activation. Differential reactivity with subsets of immature and mature T lymphocytes. J Exp Med. 1989 Jan 1;169(1):73–86. [PMC free article] [PubMed]
  • Torres-Nagel NE, Gold DP, Hünig T. Identification of rat Tcrb-V8.2, 8.5, and 10 gene products by monoclonal antibodies. Immunogenetics. 1993;37(4):305–308. [PubMed]
  • Williams AF, Galfrè G, Milstein C. Analysis of cell surfaces by xenogeneic myeloma-hybrid antibodies: differentiation antigens of rat lymphocytes. Cell. 1977 Nov;12(3):663–673. [PubMed]
  • Brideau RJ, Carter PB, McMaster WR, Mason DW, Williams AF. Two subsets of rat T lymphocytes defined with monoclonal antibodies. Eur J Immunol. 1980 Aug;10(8):609–615. [PubMed]
  • McMaster WR, Williams AF. Monoclonal antibodies to Ia antigens from rat thymus: cross reactions with mouse and human and use in purification of rat Ia glycoproteins. Immunol Rev. 1979;47:117–137. [PubMed]
  • Kupiec-Weglinski JW, Diamantstein T, Tilney NL, Strom TB. Therapy with monoclonal antibody to interleukin 2 receptor spares suppressor T cells and prevents or reverses acute allograft rejection in rats. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2624–2627. [PMC free article] [PubMed]
  • Robinson AP, White TM, Mason DW. Macrophage heterogeneity in the rat as delineated by two monoclonal antibodies MRC OX-41 and MRC OX-42, the latter recognizing complement receptor type 3. Immunology. 1986 Feb;57(2):239–247. [PMC free article] [PubMed]
  • Aarden LA, De Groot ER, Schaap OL, Lansdorp PM. Production of hybridoma growth factor by human monocytes. Eur J Immunol. 1987 Oct;17(10):1411–1416. [PubMed]
  • Mörgelin M, Heinegård D, Engel J, Paulsson M. Electron microscopy of native cartilage oligomeric matrix protein purified from the Swarm rat chondrosarcoma reveals a five-armed structure. J Biol Chem. 1992 Mar 25;267(9):6137–6141. [PubMed]
  • Oldberg A, Antonsson P, Lindblom K, Heinegård D. COMP (cartilage oligomeric matrix protein) is structurally related to the thrombospondins. J Biol Chem. 1992 Nov 5;267(31):22346–22350. [PubMed]
  • Holmdahl R. Female preponderance for development of arthritis in rats is influenced by both sex chromosomes and sex steroids. Scand J Immunol. 1995 Jul;42(1):104–109. [PubMed]
  • Månsson B, Carey D, Alini M, Ionescu M, Rosenberg LC, Poole AR, Heinegård D, Saxne T. Cartilage and bone metabolism in rheumatoid arthritis. Differences between rapid and slow progression of disease identified by serum markers of cartilage metabolism. J Clin Invest. 1995 Mar;95(3):1071–1077. [PMC free article] [PubMed]
  • Holmdahl R, Rubin K, Klareskog L, Dencker L, Gustafson G, Larsson E. Appearance of different lymphoid cells in synovial tissue and in peripheral blood during the course of collagen II-induced arthritis in rats. Scand J Immunol. 1985 Mar;21(3):197–204. [PubMed]
  • Holmdahl R, Jonsson R, Larsson P, Klareskog L. Early appearance of activated CD4+ T lymphocytes and class II antigen-expressing cells in joints of DBA/1 mice immunized with type II collagen. Lab Invest. 1988 Jan;58(1):53–60. [PubMed]
  • Janossy G, Panayi G, Duke O, Bofill M, Poulter LW, Goldstein G. Rheumatoid arthritis: a disease of T-lymphocyte/macrophage immunoregulation. Lancet. 1981 Oct 17;2(8251):839–842. [PubMed]
  • Klareskog L, Forsum U, Scheynius A, Kabelitz D, Wigzell H. Evidence in support of a self-perpetuating HLA-DR-dependent delayed-type cell reaction in rheumatoid arthritis. Proc Natl Acad Sci U S A. 1982 Jun;79(11):3632–3636. [PMC free article] [PubMed]
  • Konttinen YT, Bergroth V, Nordström D, Koota K, Skrifvars B, Hagman G, Friman C, Hämäläinen M, Slätis P. Cellular immunohistopathology of acute, subacute, and chronic synovitis in rheumatoid arthritis. Ann Rheum Dis. 1985 Aug;44(8):549–555. [PMC free article] [PubMed]
  • Fassbender HG, Simmling-Annefeld M. The potential aggressiveness of synovial tissue in rheumatoid arthritis. J Pathol. 1983 Mar;139(3):399–406. [PubMed]
  • Yoshino S, Kinne R, Hünig T, Emmrich F. The suppressive effect of an antibody to the alpha beta cell receptor in rat adjuvant arthritis: studies on optimal treatment protocols. Autoimmunity. 1990;7(4):255–266. [PubMed]
  • Goldschmidt TJ, Holmdahl R. Anti-T cell receptor antibody treatment of rats with established autologous collagen-induced arthritis: suppression of arthritis without reduction of anti-type II collagen autoantibody levels. Eur J Immunol. 1991 May;21(5):1327–1330. [PubMed]
  • Holmdahl R, Vingsbo C, Hedrich H, Karlsson M, Kvick C, Goldschmidt TJ, Gustafsson K. Homologous collagen-induced arthritis in rats and mice are associated with structurally different major histocompatibility complex DQ-like molecules. Eur J Immunol. 1992 Feb;22(2):419–424. [PubMed]
  • Wooley PH, Luthra HS, Stuart JM, David CS. Type II collagen-induced arthritis in mice. I. Major histocompatibility complex (I region) linkage and antibody correlates. J Exp Med. 1981 Sep 1;154(3):688–700. [PMC free article] [PubMed]
  • Glant TT, Mikecz K, Arzoumanian A, Poole AR. Proteoglycan-induced arthritis in BALB/c mice. Clinical features and histopathology. Arthritis Rheum. 1987 Feb;30(2):201–212. [PubMed]
  • Rook G, Thompson S, Buckley M, Elson C, Brealey R, Lambert C, White T, Rademacher T. The role of oil and agalactosyl IgG in the induction of arthritis in rodent models. Eur J Immunol. 1991 Apr;21(4):1027–1032. [PubMed]
  • Thompson HS, Harper N, Bevan DJ, Staines NA. Suppression of collagen induced arthritis by oral administration of type II collagen: changes in immune and arthritic responses mediated by active peripheral suppression. Autoimmunity. 1993;16(3):189–199. [PubMed]
  • Nordan RP, Potter M. A macrophage-derived factor required by plasmacytomas for survival and proliferation in vitro. Science. 1986 Aug 1;233(4763):566–569. [PubMed]
  • Houssiau FA, Devogelaer JP, Van Damme J, de Deuxchaisnes CN, Van Snick J. Interleukin-6 in synovial fluid and serum of patients with rheumatoid arthritis and other inflammatory arthritides. Arthritis Rheum. 1988 Jun;31(6):784–788. [PubMed]
  • Hirano T, Matsuda T, Turner M, Miyasaka N, Buchan G, Tang B, Sato K, Shimizu M, Maini R, Feldmann M, et al. Excessive production of interleukin 6/B cell stimulatory factor-2 in rheumatoid arthritis. Eur J Immunol. 1988 Nov;18(11):1797–1801. [PubMed]
  • Takai Y, Seki N, Senoh H, Yokota T, Lee F, Hamaoka T, Fujiwara H. Enhanced production of interleukin-6 in mice with type II collagen-induced arthritis. Arthritis Rheum. 1989 May;32(5):594–600. [PubMed]
  • Sugita T, Furukawa O, Ueno M, Murakami T, Takata I, Tosa T. Enhanced expression of interleukin 6 in rat and murine arthritis models. Int J Immunopharmacol. 1993 May;15(4):469–476. [PubMed]
  • Hitsumoto Y, Thompson SJ, Zhang YW, Rook GA, Elson CJ. Relationship between interleukin 6, agalactosyl IgG and pristane-induced arthritis. Autoimmunity. 1992;11(4):247–254. [PubMed]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem Compound links
  • Gene
    Gene links
  • MedGen
    Related information in MedGen
  • OMIM
    OMIM record citing PubMed
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...