ab17_3

Tissue distribution and persistence of arthritogenic and non-arthritogenic Eubacterium cell walls

E. Simelyte, M. Rimpiläinen, K. Rantakokko, L. Lehtonen, X. Zhang, H. Aho¹, P. Isomäki, P. Toivanen

Turku Immunology Centre, Departments of Medical Microbiology and ¹Pathology, Turku University, Turku, Finland.

ABSTRACT
Objective
To study the tissue distribution and persistence of arthritogenic and non-arthritogenic Eubacterium cell walls (CWs), using arthritogenic Eubacterium aerofaciens and non-arthritogenic Eubacterium limosum.

Methods
Eubacterium aerofaciens or Eubacterium limosum CW was injected into Lewis rats intraperitoneally. Inflammatory changes in the synovium and periarticular tissues were graded histologically. On days 14, 28 and 56 after the injection, the presence of CW in the liver, spleen, mesenteric lymph nodes and synovium was studied by indirect immunofluorescence. In parallel, CW-derived muramic acid in the liver and spleen was measured by gas chromatography-mass spectrometry. In addition, serum TNF-a, IL-1b and IL-10 concentrations were determined by ELISA.

Results
Systemic injection of Eubacterium aerofaciens CW, but not of Eubacterium limosum CW, resulted in chronic arthritis. Both E. aerofaciens and E. limosum CWs were observed in the liver and spleen at all of the time points studied. In addition, Eubacterium limosum CW was present in non-arthritic synovium on day 14. It was not, however, detected in the synovium or lymph nodes on days 28 and 56, in clear contrast to the rats injected with E. aerofaciens CW. According to the analysis by gas chromatography-mass spectrometry, non-arthritogenic E. limosum CW had accumulated in the liver cells on days 14 and 28 after the injection to a greater extent than arthritogenic E. aerofaciens CW, leading to a lesser distribution in the other organs. A weak trend was observed suggesting that the production of TNF-a and IL-1b, but not of IL-10, is stimulated better by arthritogenic CW than by non-arthritogenic CW.

Conclusion
Our results indicate that non-arthritogenic CWs are handled by the rat’s defence mechanisms in a different way than arthritogenic CWs. The tissue distribution and persistence of CWs play a role in arthritogenicity, but additional factors must exist to determine why the CWs of certain bacteria are arthritogenic and those of others are not.

Key words
Rheumatoid arthritis, Eubacterium cell wall, IL-1b, IL-10, muramic acids, inbred LEW rats, TNF-a.

This work was supported by the Academy of Finland.

Please address correspondence and reprint requests to: Dr. Egle Simelyte, Department of Medical Microbiology, Kiinamyllynkatu 13, FIN-20520 Turku, Finland.