T-cell mediated inflammatory joint diseases with similarities to rheumatoid arthritis can be triggered in arthritis-prone rat strains by intradermal injection of adjuvant-oils. The pathogenesis of oil-induced arthritis (OIA) remains elusive, and a largely unresolved question concerns how the rat immune system responds to arthritogenic oils, such as incomplete Freund's adjuvant (IFA). Here we report that IFA induces increased plasma levels of the APR (acute phase reactants) fibrinogen and AGP (a1-acid glycoprotein) already at day 4 post-injection (d.p.i.). In contrast, no early responses were detected in the joints before infiltration of T-cells, which coincided with arthritis onset at 11-14 d.p.i. The infiltrating cells were possibly derived from draining lymph nodes (LN), which contained dramatically increased cell numbers from 4 d.p.i. onwards. The magnitude of the early increase in cell numbers and APR was regulated by non-MHC genes, as determined by comparison between arthritis-susceptible DA rats and arthritis-resistant but MHC-identical LEW.1AV1 and PVG.1AV1 rats. These resistant strains had high plasma AGP at 4 d.p.i. whereas DA rats did not - possibly reflecting a deficient anti-inflammatory response in this strain. Furthermore, the relative increase in LN cell numbers was largest in DA rats, which is intriguing considering that LN T-cells can transfer arthritis. Analysis of LN after in vivo labelling with BrdU revealed increased numbers and proportions of proliferating lymphocytes. Furthermore, PCR-analysis of LN cytokine mRNA revealed up regulation for IL-1b at 4 d.p.i. When an immunogen (ovalbumin) was added to the adjuvant an immune response was clearly traced as increased mRNA for IL-4, IFN-g and IL-1b, and in increased numbers of proliferating lymphocyte in vivo.
In summary, we provide evidence that arthritogenic oil induces an early systemic inflammatory response, as well as activation of cells and lymphocytes in draining lymph nodes, but no signs of cell activation in the joints before onset of arthritis.