Abstract
Inbred female Lewis (LEW/N) rats develop a severe chronic arthritis in the adjuvant arthritis (AA) model, histocompatible Fisher (F344/N) rats are resistant and germ-free Fishers (GF F344) are again susceptible. In this study we show that the F344 rat can become susceptible to AA, using Mycobacterium tuberculosis (M.tb.) in the powerful adjuvant paraffin oil, instead of mineral oil (Freund's incomplete adjuvant (FIA)). This indicates that the F344 rat does not lack T effector cells. To examine further mechanisms responsible for suppression, we determined the level of plasma corticosterone in response to IL-1 alpha in Lewis, F344 and GF F344 rats. IL-1 alpha induced only low amounts of corticosterone in Lewis rats, but high amounts in both F344 and GF F344 rats. The GF F344 rats are susceptible to AA, but the severity of the disease is reduced compared with Lewis rats. This indicates that corticosterone may be an important mechanism to suppress disease development, but not the only mechanism. In addition we investigated whether T suppressor cells play a role in the resistance of the F344 strain. This was performed by pretreating the animals with the immunomodulating drugs cyclophosphamide (Cy) and cyclosporin A (CsA). We were unable to make the F344 rat susceptible to AA, indicating that active suppression does not play a role in the induction phase of arthritis. This finding is confirmed in adoptive transfer experiments of AA from Lewis to F344 rats. Our data suggest the lack of a strong pre-existing suppression in the F344 rats, and indicate that suppression is generated upon bacterial challenge. Whether suppression is overruled probably depends on the power of adjuvants used and potential control by corticosteroids.