Combined Effects of IL-12 and IL-18 on the Induction of Collagen-Induced Arthritis1
Combined Effects of IL-12 and IL-18 on the Induction of Collagen-Induced Arthritis1
复制标题
IL-12 和 IL-18 对胶原诱导关节炎的联合作用1
作者：
B. Leung;I. McInnes;E. Esfandiari;Xiao‐qing Wei;F. Liew
IL-18的表达最近在类风湿关节炎（RA）滑膜中检测到。我们研究了il -18诱导的DBA/1小鼠胶原诱导关节炎的机制，在IFA中皮内注入II型牛胶原，并在21天后用盐水中CII促进i.p。小鼠分别在第1 - 4天和第20-24天分别腹腔注射il -12、il -18或两者均注射（100 ng）。对照组小鼠接受PBS治疗。与对照组相比，单独使用IL-12或IL-18治疗的小鼠发病率更高，疾病更严重。通过与IL-12和IL-18联合治疗，这些水平进一步升高。与对照组相比，细胞因子治疗显著增强了滑膜增生、细胞浸润和软骨侵蚀。细胞因子处理的小鼠比对照组产生更多的IFN-γ、TNF-α和IL-6。有趣的是，与IL-12处理的小鼠相比，il -18处理的小鼠产生更多的TNF-α和IL-6，但较少的IFN-γ。此外，体外培养IL-18而非IL-12的DBA/1小鼠脾巨噬细胞产生大量TNF-α。与对照组相比，IL-18或IL-18加IL-12处理的小鼠产生了更多的IgG1和IgG2a抗胶原抗体，而IL-12处理仅导致IgG2a反应增强。总之，这些结果表明，IL-18可以通过不同于IL-12诱导的机制促进胶原诱导的炎症性关节炎。
IL-18 expression has recently been detected in rheumatoid arthritis (RA) synovial membrane. We investigated the mechanisms by which IL-18-induced collagen-induced arthritis in DBA/1 mice primed intradermally with type II bovine collagen in IFA and boosted i.p. 21 days later with CII in saline. Mice were injected i.p. with rIL-12, rIL-18, or both (100 ng) during days −1 to 4 and again on days 20–24. Control mice received PBS. Mice treated with IL-12 or IL-18 alone developed significantly higher incidence and more severe disease compared with controls. These were elevated further by combination treatment with IL-12 and IL-18. The cytokine treatments led to markedly enhanced synovial hyperplasia, cellular infiltration, and cartilage erosion compared with controls. Cytokine-treated mice produced significantly more IFN-γ, TNF-α, and IL-6 than the controls. Interestingly, IL-18-treated mice produced more TNF-α and IL-6, but less IFN-γ, compared with mice treated with IL-12. Furthermore, splenic macrophages from DBA/1 mice cultured in vitro with IL-18, but not IL-12, produced substantial amounts of TNF-α. Mice treated with IL-18 or IL-18 plus IL-12 produced markedly more IgG1 and IgG2a anti-collagen Ab compared with controls, whereas IL-12 treatment only led to an enhanced IgG2a response. Together these results demonstrate that IL-18 can promote collagen-induced inflammatory arthritis through mechanisms that may be distinct from those induced by IL-12.
Hoshino T：“IL-18 是 NK 和 T 细胞中 IL-13 的有效共诱导物：IL-18 在调节免疫反应中的新潜在作用。”J.Immunol.. 162. 5070-5077 (1999)
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影响因子：
4.4
作者：
T. Olee;S. Hashimoto;J. Quach;M. Lotz
通讯作者：
T. Olee;S. Hashimoto;J. Quach;M. Lotz
影响因子：
15.9
作者：
Puren, AJ;Fantuzzi, G;Dinarello, CA
通讯作者：
Dinarello, CA