title: 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.
authors.affiliation: Department of Medical Microbiology, University College, Middlesex School of Medicine, London.
authors.forename: G
authors.initials: G
authors.lastname: Rook
authors.forename: S
authors.initials: S
authors.lastname: Thompson
authors.forename: M
authors.initials: M
authors.lastname: Buckley
authors.forename: C
authors.initials: C
authors.lastname: Elson
authors.forename: R
authors.initials: R
authors.lastname: Brealey
authors.forename: C
authors.initials: C
authors.lastname: Lambert
authors.forename: T
authors.initials: T
authors.lastname: White
authors.forename: T
authors.initials: T
authors.lastname: Rademacher
mesh_terms: D000818:Animals; D001168:Arthritis / Q000209:etiology*; D003094:Collagen / Q000276:immunology; D006360:Heat-Shock Proteins / Q000494:pharmacology; D007074:Immunoglobulin G / Q000032:analysis / Q000502:physiology*; D015850:Interleukin-6 / Q000502:physiology; D051379:Mice; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D009821:Oils / Q000633:toxicity*; D013729:Terpenes / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D006360:Heat-Shock Proteins; D007074:Immunoglobulin G; D015850:Interleukin-6; D009821:Oils; D013729:Terpenes; D014409:Tumor Necrosis Factor-alpha; C064155:agalactosyl IGG; C009042:pristane; D003094:Collagen