Molecular and cellular mediators of interleukin-1-dependent acute inflammatory arthritis
- Author(s)
- Lawlor, KE; Campbell, IK; O'Donnell, K; Wu, L; Wicks, IP;
- Details
- Publication Year 2001-02,Volume 44,Issue #2,Page 442-450
- Journal Title
- ARTHRITIS AND RHEUMATISM
- Publication Type
- Journal Article
- Abstract
- Objective. To examine the molecular and cellular mechanisms in a model of acute inflammatory monarticular arthritis induced by methylated bovine serum albumin (mBSA) and interleukin-1 (IL-1). Methods. Mice were injected intraarticularly with mBSA on day 0 and subcutaneously with recombinant human IL-1 beta on days 0-2. At day 7, knee joints were removed and assessed histologically. Flow cytometry and RNase protection were used to analyze IL-1-dependent events. Results. C57BL/6 (B6), 129/Sv, and (B6 x 129/Sv)F-1 hybrid mice, all H-2(b) strains, were susceptible to mBSA/IL-1-induced arthritis, whereas C3H/HeJ (H-2(k)) mice were not. B6 mice lacking T and B cells (RAG-1(-/-)) or major histocompatibility complex (MHC) class II antigens (MHCII-/-), and B6 mice treated with a CD4+ T cell-depleting monoclonal antibody, were resistant to disease. In contrast, B cell-deficient (mu MT/mu MT) mice developed arthritis at an incidence and severity similar to that of controls. ReIB-deficient (ReIB-/-) bone marrow chimeric mice had arthritis that was significantly reduced in incidence and severity. In B6 mice, flow cytometry demonstrated an IL-1-dependent leukocyte infiltration into the synovial compartment and RNase protection assays revealed induction of messenger RNA (mRNA) for the chemokines monocyte chemoattractant protein 1, macrophage inhibitory protein 2 (MIP-2), RANTES, MIP-1 alpha, and MIP-1 beta, in vivo and in vitro. Conclusion. Arthritis induced by mBSA/IL-1 is strain specific and dependent on CD4+ T lymphocytes and at least partially on ReIB, but not on B lymphocytes or antibody. IL-1 contributes to leukocyte recruitment to the synovium and directly induces chemokine mRNA production by synovial cells. This model of acute monarticular arthritis is particularly suitable for further investigations into cell-mediated immunity in arthritis and the role of IL-1.
- Publisher
- WILEY-LISS
- Keywords
- COLLAGEN-INDUCED ARTHRITIS; ANTIGEN-INDUCED ARTHRITIS; RHEUMATOID-ARTHRITIS; TARGETED DISRUPTION; DENDRITIC CELLS; T-CELLS; DEFICIENT MICE; LYMPHOCYTES-T; RELB; CHEMOKINES
- Publisher's Version
- https://doi.org/10.1002/1529-0131(200102)44:2<442::AID-ANR63>3.0.CO;2-M
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- Refer to copyright notice on published article.
Creation Date: 2001-02-01 12:00:00