- Meeting abstract
- Open Access
- Published:
Role of Cytokines in Cartilage Destruction in Experimental Arthritis
Arthritis Research & Therapy volume 1, Article number: S29 (1999)
Full text
Rheumatoid arthritis (RA) is characterized by major destruction of the articular cartilage. The mediators TNFα and IL-1 probably play a major role in RA. Following studies in experimental murine arthritis models, using neutralising antibodies and scavenging receptors, it became clear that TNF is a major inflammatory cytokine, whereas IL-1 is the main destructive cytokine. These observations were recently confirmed using TNF and IL-1 knock-out mice. Remarkably, arthritis in TNF-deficient mice was strongly reduced, and yet ongoing cartilage destruction was still noted. In contrast, cartilage destruction was minimal in IL-1β knock-out mice.
Apart from inhibition of IL-1, major therapeutic benefit can be achieved with IL-4 and IL-10 treatment. These cytokines reduce IL-1 levels and relatively enhance IL-ra. Local gene transfer with adenoviral IL-4 constructs revealed major protection against cartilage and bone erosions in experimental arthritis despite marked inflammation.
Stromelysin seems a pivotal enzyme involved in cartilage breakdown. It is not an essential MMP in the early proteoglycan loss, and a major role for aggrecanase seems obvious. However, stromelysin seems crucial in collagenase activation and collagen breakdown, and irreversible cartilage erosion is markedly reduced in arthritis in stromelysin knock-out mice. Induction of stromelysin-induced neoepitopes and late destruction can be blocked with IL-1 neutralization.
References
- 1.
Van den Berg WB: Joint inflammation and cartilage destruction may occur uncoupled. Springer Semin Immunopathol. 1998, 20: 149-164. 10.1007/BF00832004.
- 2.
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. 10.1002/1529-0131(199804)41:4<647::AID-ART11>3.3.CO;2-K.
- 3.
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-TNFα, anti-IL-1α/β, and IL-1ra. Arthritis Rheum. 1996, 39: 797-809.
- 4.
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: 4546-4556.
Author information
Affiliations
Rights and permissions
About this article
Cite this article
van den Berg, W.B. Role of Cytokines in Cartilage Destruction in Experimental Arthritis. Arthritis Res Ther 1, S29 (1999). https://doi.org/10.1186/ar43
Published:
Keywords
- Cartilage Destruction
- Experimental Arthritis
- Cartilage Breakdown
- Proteoglycan Loss
- Pivotal Enzyme
