Blockade of IL‐12 during the induction of collagen‐induced arthritis (CIA) markedly attenuates the severity of the arthritis
Blockade of IL‐12 during the induction of collagen‐induced arthritis (CIA) markedly attenuates the severity of the arthritis
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DOI：
10.1046/j.1365-2249.1998.00485.x
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发表时间：
1998-02
影响因子：
4.6
通讯作者：
A. Malfait;D. M. Butler;D. Presky;R. Maini;F. Brennan;Marc Feldmann
中科院分区：
文献类型：
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作者：
A. Malfait;D. M. Butler;D. Presky;R. Maini;F. Brennan;Marc Feldmann
研究了在CIA诱导期阻断IL-12（干扰素-γ（IFN-γ）的强效诱导剂和Th 1细胞应答的启动子）的作用。通过用弗氏完全佐剂中的II型胶原（CII）免疫雄性DBA/1小鼠引起关节炎。从CII免疫开始，每周两次给予中和抗IL-12抗体。研究发现，从免疫接种到临床关节炎发作期间给予抗IL-12并没有降低关节炎的发病率，但在临床和组织病理学上显著减轻了疾病的严重程度。该方案与离体CII刺激的引流淋巴结细胞产生的IFN-γ水平降低以及新鲜分离的滑膜细胞自发离体产生的肿瘤坏死因子（TNF）、IL-6和IL-10减少相关。这些小鼠中的总抗CII抗体血清水平低于对照组，但IgG 2a/IgG 1比值无变化。这些发现证实了IL-12在诱导小鼠CIA中具有重要作用，并表明这种疾病部分由Th 1表型细胞传播。
The effect of blocking IL‐12, a potent inducer of interferon‐gamma (IFN‐γ) and promoter of Th1 cell responses, during the induction phase of CIA was investigated. Arthritis was elicited in male DBA/1 mice by immunizing with type II collagen (CII) in Freund's complete adjuvant. Neutralizing anti‐IL‐12 antibodies were administered twice weekly from CII immunization. It was found that administration of anti‐IL‐12 from immunization until the onset of clinical arthritis did not lower the incidence of arthritis, but dramatically attenuated the severity of the disease, both clinically and histopathologically. This regime was associated with reduced IFN‐γ levels produced by ex vivo CII‐stimulated draining lymph node cells, and with diminished spontaneous ex vivo production of tumour necrosis factor (TNF), IL‐6 and IL‐10 by freshly isolated synovial cells. Total anti‐CII antibody serum levels in these mice were lower than in the controls, but there was no change in the IgG2a/IgG1 ratio. These findings confirm that IL‐12 has a major role in the induction of murine CIA and suggests that this disease is propagated, in part, by cells of the Th1 phenotype.