The Importance of IL-1β and TNF-α, and the Noninvolvement of IL-6, in the Development of Monoclonal Antibody-Induced Arthritis
- 1 August 2002
- journal article
- Published by Oxford University Press (OUP) in The Journal of Immunology
- Vol. 169 (3) , 1459-1466
- https://doi.org/10.4049/jimmunol.169.3.1459
Abstract
Injection of anti-type II collagen Ab and LPS induces arthritis in mice. The levels of IL-1β, IL-6, and chemokines (macrophage inflammatory protein (MIP)-1α, MIP-2, and monocyte chemoattractant protein-1) in the hind paws increased with the onset of arthritis and correlated highly with arthritis scores. The level of TNF-α was also elevated, but only transiently. Quantitative real-time PCR analysis revealed increases in cytokine and chemokine mRNA. To elucidate the contribution of inflammatory cytokines and chemokines in arthritis development more directly, recombinant proteins, neutralizing Abs, and knockout mice were used. The injection of rIL-1β or TNF-α, but not IL-6 or chemokines, induced arthritis when mice were i.v. preinjected with anti-type II collagen Ab. However, a single injection of recombinant cytokines or chemokines into the hind paws did not induce swelling. Arthritis development was inhibited by neutralizing Ab against IL-1β, TNF-α, or MIP-1α. In contrast, the inhibitory effect by anti-MIP-2 Ab was partial and, surprisingly, Abs to IL-6 and monocyte chemoattractant protein-1 showed no inhibitory effect. Furthermore, arthritis development in IL-1R−/− mice and TNFR−/− mice was not observed at all, but severe arthritis was developed in IL-6−/− mice. These results suggest that IL-1β and TNF-α play more crucial roles than IL-6 or chemokines in this model. Because arthritis was also developed in SCID mice, the development of arthritis in the Ab-induced mice model is due to a mechanism that does not involve T or B cells.Keywords
This publication has 40 references indexed in Scilit:
- Human chondrocytes express functional chemokine receptors and release matrix-degrading enzymes in response to C-X-C and C-C chemokinesArthritis & Rheumatism, 2000
- Collagen-induced arthritis development requires αβ T cells but not γδ T cells: studies with T cell-deficient (TCR mutant) miceInternational Immunology, 1999
- Dynamics of proinflammatory cytokine expression in the joints of mice with collagen-induced arthritis (CIA)Clinical and Experimental Immunology, 1997
- Collagen-Induced Arthritis in Mice: Synergistic Effect of E. Coli Lipopolysaccharide Bypasses Epitope Specificity in the Induction of Arthritis with Monoclonal Antibodies to Type II CollagenAutoimmunity, 1995
- Impaired immune and acute-phase responses in interleukin-6-deficient miceNature, 1994
- Macrophage inflammatory protein-1 alpha. A novel chemotactic cytokine for macrophages in rheumatoid arthritis.Journal of Clinical Investigation, 1994
- Tumor necrosis factor Characterization at the molecular, cellular and in vivo levelFEBS Letters, 1991
- The essential role of B cell stimulatory factor 2 (BSF-2/IL-6) for the terminal differentiation of B cells.The Journal of Experimental Medicine, 1988
- An interleukin 1 like factor stimulates bone resorption in vitroNature, 1983
- Immunisation against heterologous type II collagen induces arthritis in miceNature, 1980