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.