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Adenoviral Vector-Mediated Overexpression of IL-4 in the Knee Joint of Mice with Collagen-Induced Arthritis Prevents Cartilage Destruction
Abstract
Rheumatoid arthritis is a chronic inflammatory joint disease, leading to cartilage and bone destruction. In this study, we investigated the effects of local IL-4 application, introduced by a recombinant human type 5 adenovirus vector, in the knee joint of mice with collagen-induced arthritis. One intraarticular injection with an IL-4-expressing virus caused overexpression of IL-4 in the mouse knee joint. Enhanced onset and aggravation of the synovial inflammation were found in the IL-4 group. However, despite ongoing inflammation, histologic analysis showed impressive prevention of chondrocyte death and cartilage erosion. In line with this, chondrocyte proteoglycan synthesis was enhanced in the articular cartilage. This was quantified with ex vivo 35S-sulfate incorporation in patellar cartilage and confirmed by autoradiography on whole knee joint sections. Reduction of cartilage erosion was further substantiated by lack of expression of the stromelysin-dependent cartilage proteoglycan breakdown neoepitope VDIPEN in the Ad5E1 mIL-4-treated knee joint. Reduced metalloproteinase activity was also supported by markedly diminished mRNA expression of stromelysin-3 in the synovial tissue. Histologic analysis revealed marked reduction of polymorphonuclear cells in the synovial joint space in the IL-4-treated joints. This was confirmed by immunolocalization studies on knee joint sections using NIMP-R14 staining and diminished mRNA expression of macrophage-inflammatory protein-2 in the synovium tissue. mRNA levels of TNF-α and IL-1β were suppressed as well, and IL-1β and nitric oxide production by arthritic synovial tissue were strongly reduced. Our data show an impressive cartilage-protective effect of local IL-4 and underline the feasibility of local gene therapy with this cytokine in arthritis.
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Elliott, M. J., Maini, R. N., Feldmann, M., Kalden, J. R., Antoni, C., Smolen, J. S., Leeb, B., Breedveld, F. C., Macfarlane, J. D., Bijl, J. A., et al. (1994) · The Lancet · doi:10.1016/s0140-6736(94)90628-9 · Cited by 1,682
Cited by
Lubberts, E., Joosten, L. A. B., Oppers, B., van den Bersselaar, L., Coenen-de Roo, C. J. J., Kolls, J. K., Schwarzenberger, P., van de Loo, F. A. J., & van den Berg, W. B. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.2.1004 · Cited by 401
Self-citationLubberts, E., Joosten, L. A. B., Chabaud, M., van den Bersselaar, L., Oppers, B., Coenen-de Roo, C. J. J., Richards, C. D., Miossec, P., & van den Berg, W. B. (2000) · Journal of Clinical Investigation · doi:10.1172/jci7739 · Cited by 309
Self-citationIL-17/Th17 targeting: On the road to prevent chronic destructive arthritis?
Lubberts, E. (2008) · Cytokine · doi:10.1016/j.cyto.2007.09.014 · Cited by 289
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Metadata
- Authors
- Lubberts, E., Joosten, L. A. B., van den Bersselaar, L., Helsen, M. M. A., Bakker, A. C., van Meurs, J. B. J., Graham, F. L., Richards, C. D., & van den Berg, W. B.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1999-10
- Volume
- 163
- Issue
- 8
- Pages
- 4546-4556
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1887346136
- Cited by
- 179
- References
- 1
- FWCI
- 13.55
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Adenoviral Vector-Mediated Overexpression of IL-4 in the Knee Joint of Mice with Collagen-Induced Arthritis Prevents Cartilage Destruction. https://app.cochat.ai/papers/10.4049/jimmunol.163.8.4546
- The paper
- Lubberts, E., Joosten, L. A. B., van den Bersselaar, L., Helsen, M. M. A., Bakker, A. C., van Meurs, J. B. J., Graham, F. L., Richards, C. D., & van den Berg, W. B. (1999). Adenoviral Vector-Mediated Overexpression of IL-4 in the Knee Joint of Mice with Collagen-Induced Arthritis Prevents Cartilage Destruction. The Journal of Immunology. https://doi.org/10.4049/jimmunol.163.8.4546
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
