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The role of oil and agalactosyl IgG in the induction of arthritis in rodent models.

Abstract
The proportion of agalactosyl IgG [Gal(O)] is raised in human rheumatoid arthritis and tuberculosis. We report here that injection of pristane into the peritoneal cavities of mice on days 0 and 50, which is known to induce plasmacytomas and arthritis, also induced a rise in the proportion of Gal(O), correlating with a simultaneous rise in the level of IgG antibody binding to the 65-kDa heat-shock protein of Mycobacterium bovis (hsp65). Arthritis developed in a proportion of those CBA/Igb mice with the highest percentage of Gal(O). Pretreatment with 50 micrograms of recombinant mycobacterial hsp65 intraperitoneal (i.p.) on day -10, or with 500 rad irradiation on day -2 before the first of the two injections of pristane reduced the incidence of arthritis from 24% in control animals, to 5.3% and 0.4%, respectively. The reduced incidence of disease correlated with smaller rises in the % Gal(O) at 50-75 days, although levels at 150-200 days were not affected. The arthritogenic effect of oil was not confined to the pristane model, since a single i.p. injection of oil 21 days before immunizing DBA/1 mice with type II collagen reduced the mean day of onset of this arthritis, [which we have previously shown to correlate with raised % Gal(O)], from 38 to 15 days (p less than 0.001). One interpretation is that an autoimmunogenic stimulus, given when % Gal(O) is raised, is more likely to evoke disease. Since oil granulomata are known to secrete interleukin 6, which has B cell-regulatory properties and is secreted by rheumatoid synovial cells, we tested sera from interleukin 6-transgenic mice, and found a strikingly raised percentage of Gal(O). We suggest, therefore, that the role of oil in the induction of arthritis is the dysregulation of cytokine release of which a raised percentage of Gal(O) may be a direct or indirect consequence, associated with an increased susceptibility to autoimmunogenic stimuli.
AuthorsG Rook, S Thompson, M Buckley, C Elson, R Brealey, C Lambert, T White, T Rademacher
JournalEuropean journal of immunology (Eur J Immunol) Vol. 21 Issue 4 Pg. 1027-32 (Apr 1991) ISSN: 0014-2980 [Print] Germany
PMID2019285 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Heat-Shock Proteins
  • Immunoglobulin G
  • Interleukin-6
  • Oils
  • Terpenes
  • Tumor Necrosis Factor-alpha
  • agalactosyl IGG
  • pristane
  • Collagen
Topics
  • Animals
  • Arthritis (etiology)
  • Collagen (immunology)
  • Heat-Shock Proteins (pharmacology)
  • Immunoglobulin G (analysis, physiology)
  • Interleukin-6 (physiology)
  • Mice
  • Mice, Inbred CBA
  • Mice, Inbred DBA
  • Oils (toxicity)
  • Terpenes (pharmacology)
  • Tumor Necrosis Factor-alpha (physiology)

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