The importance of IL-1β and TNF-α, and the noninvolvement of IL-6, in the development of monoclonal antibody-induced arthritis
The importance of IL-1β and TNF-α, and the noninvolvement of IL-6, in the development of monoclonal antibody-induced arthritis
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DOI：
10.4049/jimmunol.169.3.1459
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发表时间：
2002-08-01
影响因子：
4.4
通讯作者：
Shimozato, T
中科院分区：
文献类型：
--
作者：
Kagari, T;Doi, H;Shimozato, T
注射抗 II 型胶原抗体和 LPS 可诱导小鼠关节炎。 The levels of IL-1beta, IL-6, and chemokines (macrophage inflammatory protein (MIP)-1alpha, MIP-2, and monocyte chemoattractant protein-1) in the hind paws increased with the onset of arthritis and correlated highly with arthritis scores. TNF-α 的水平也升高，但只是短暂的。实时定量 PCR 分析显示细胞因子和趋化因子 mRNA 增加。 To elucidate the contribution of inflammatory cytokines and chemokines in arthritis development more directly, recombinant proteins, neutralizing Abs, and knockout mice were used.当小鼠静脉注射 rIL-1beta 或 TNF-α（而非 IL-6 或趋化因子）时，会诱发关节炎。预注射抗11型胶原抗体。然而，将重组细胞因子或趋化因子单次注射到后爪中并不会引起肿胀。中和针对 IL-1β、TNF-α 或 MIP-1α 的抗体可抑制关节炎的发展。 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.这些结果表明，在该模型中，IL-1β 和 TNF-a 比 IL-6 或趋化因子发挥更重要的作用。 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.
Injection of anti-type II collagen Ab and LPS induces arthritis in mice. The levels of IL-1beta, IL-6, and chemokines (macrophage inflammatory protein (MIP)-1alpha, 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-alpha 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-1beta or TNF-alpha, but not IL-6 or chemokines, induced arthritis when mice were i.v. preinjected with anti-type 11 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-1beta, TNF-alpha, or MIP-1alpha. 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-1beta and TNF-a 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.