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Rheumatology 2001; 40: 438-446
© 2001 British Society for Rheumatology

Peptidoglycan from sterile human spleen induces T-cell proliferation and inflammatory mediators in rheumatoid arthritis patients and healthy subjects

I. A. Schrijver, M.-J. Melief, H. M. Markusse1, I. Van Aelst2, G. Opdenakker2, M. P. Hazenberg and J. D. Laman

Department of Immunology, Erasmus University Rotterdam,
1 Department of Rheumatology, Zuiderziekenhuis, Rotterdam, The Netherlands and
2 Rega Institute for Medical Research, Laboratory of Molecular Immunology, University of Leuven, Belgium

Objectives. Peptidoglycan (PG), a component of Gram-positive bacteria, may be involved in rheumatoid arthritis (RA) because of its ability to induce production of proinflammatory cytokines, to induce arthritis in rodents, and its presence in antigen-presenting cells in RA joints.

Methods. In the present study, physiologically relevant PG was able to induce T-cell proliferation in peripheral blood and synovial fluid samples of RA patients, but the magnitude of the response did not differ from that of cells from healthy subjects. In addition, production of cytokines associated with RA (interleukins (IL)-1ß, IL-6, IL-8, IL-10, IL-12 and tumour necrosis factor {alpha}) and of the matrix metalloproteinase, gelatinase B (MMP-9), was induced in blood and synovial fluid cultures of RA patients.

Conclusion. The fact that PG, which can be found in synovial tissues of RA patients is able to induce the production of inflammatory mediators supports the hypothesis that PG plays a role in the pathogenesis of RA by influencing the inflammatory microenvironment of the joint.

KEY WORDS: Peptidoglycan, Rheumatoid arthritis, Cytokines, Matrix metalloproteinases, T cells, Bacteria, Gut.

Correspondence to: J. D. Laman, Department of Immunology, Erasmus University Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands.


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