Regulation of resistance against adjuvant arthritis in the Fisher rat

Author:

van de LANGERIJT A G M1,van LENT P L E M1,HERMUS A R M M2,van de PUTTE L B A1,van den BERG W B1

Affiliation:

1. Department of Rheumatology, Experimental Endocrinology, University Hospital Nijmegen, Nijmegen, The Netherlands

2. Department of Chemical and Experimental Endocrinology, University Hospital Nijmegen, Nijmegen, The Netherlands

Abstract

SUMMARY 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 Mycobavterium 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 nol lack T effector cells. To examine further mechanisms responsible for suppression, we determined the level of plasma eorticosterone in response to IL-1α in Lewis. F344 and GF F344 rats. IL-lα induced only low amounts of corticosterone in Lewis rats, but high amounts in both F344and GF F344 rats. The GF F344 rats are susceptible lo AA. but the severity of the disease is redueed compared with Lewis rats. This indicates that corticosterone may be an important mechanism lo 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 immunomodu-laling drugs cyelophosphamide (Cy) and cyclosporin A (CsA). We were unable to make the F344 rat susceptible to AA, indicating that active suppression does nol 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 dala 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.

Publisher

Oxford University Press (OUP)

Subject

Immunology,Immunology and Allergy

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