Rheumatoid Arthritis is a Lining Cell Disease: An Evolving Concept

  • Leo BA van de Putte1,

    Affiliated with

    • PLEM van Lent1,

      Affiliated with

      • RJT Rodenburg1,

        Affiliated with

        • P Barrera1,

          Affiliated with

          • Walther J van Venrooij1 and

            Affiliated with

            • Wim B van den Berg1

              Affiliated with

              Arthritis Res19991(Suppl 1):S17

              DOI: 10.1186/ar31

              Published: 15 November 1999

              Full text

              Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting predominantly lining structures, including synovial tissue, tendon sheaths, bursae, pleura, and pericardium. Characteristically, these tissues contain large numbers of macrophages, suggesting that these cells are crucial in the pathogenesis of the disease. Data obtained by us and by others have indicated that phagocytic lining cells are essential for disease onset and expression. Removal of synovial lining cells by intra-articular injection of apoptosis-inducing clodronate liposomes prevents joint inflammation in murine arthritis models, and pilot data suggest that these liposomes can be succesfully used in humans. The degree of monocyte/macrophage (but not of T-cell) infiltration in rheumatoid joints has been reported to correlate with both disease activity and progression of joint destruction in rheumatoid arthritis (RA). Recent studies have shown that intrinsic macrophage characteristics may determine an individual's susceptibility to develop arthritis. Murine collagen-induced arthritis-susceptible mouse strains were shown to have markedly higher expression of FcK RII/III by macrophages than nonsusceptible strains (Blom, 1999). In human RA, we found that activated monocyte-derived macrophages produce significantly higher IL-8 mRNA levels than those in controls, pointing to an innate hyper-responsiveness of these cells in this disease. The central role of lining macrophages in the pathogenesis of RA has therapeutic consequences in terms of targeting these cells and/or their proinflammatory products.

              Authors’ Affiliations

              (1)
              University Hospital Nijmegen

              References

              1. Joosten LAB, Helsen MMA, van de Loo FAJ, van den Berg WB: Anti-cytokine treatment of established type II collagen-induced arthritis in DBA/1 mice: a comparative study using anti-TNFI, anti-IL-1I/β, and IL-1ra. Arthritis Rheum 1996, 39:797–809.View ArticlePubMed
              2. Joosten LAB, Lubberts E, Durez P, Helsen MMA, Jacobs MJM, Goldman M, van den Berg WB: Role of IL-4 and IL-10 in murine collagen-induced arthritis: Protective effect of IL-4 and IL-10 treatment on cartilage destruction. Arthritis Rheum 1997, 40:249–260.View ArticlePubMed
              3. Kuiper S, Joosten LAB, Bendele AM, et al.: Different roles of TNFI and IL-1 in murine streptococcal cell wall arthritis. Cytokine 1998, 10:690–702.View ArticlePubMed
              4. Van Meurs JBJ, van Lent PLEM, Singer II, Bayne EK, van de Loo FAJ, van den Berg WB: IL-1ra prevents expression of the metalloproteinase-generated neoepitope VDIPEN in antigen-induced arthritis. Arthritis Rheum 1998, 41:647–656.View ArticlePubMed
              5. Van Meurs JBJ, van Lent PLEM, Holthuysen AEM, Singer II, Bayne EK, van den Berg WB: Kinetics of aggrecanase and metalloproteinase induced neoepitopes in various stages of cartilage destruction in murine arthritis. Arthritis Rheum 1999, 42:1128–1139.View ArticlePubMed
              6. Lubberts E, Joosten LAB, van den Bersselaar L, et al.: Adenoviral vector-mediated overexpression of IL-4 in the knee joint of mice with collagen-induced arthritis prevents cartilage destruction. J Immunol 1999, 163:4546–56.PubMed

              Copyright

              © Current Science Ltd 2000

              Advertisement