Hagiwara E, Okubo T, Aoki I, Ohno S, Tsuji T, Ihata A, Ueda A, Shirai A, Okuda K, Miyazaki J, Ishigatsubo Y
Department of Internal Medicine, Yokohama City University of Medical School, Yokohama, Japan.
Cytokine. 2000 Jul;12(7):1035-41. doi: 10.1006/cyto.1999.0662.
Systemic lupus erythematosus (SLE) is characterized by immune abnormalities explained by the overproduction of Th(2)cytokines such as autoantibody production and polyclonal B cell activation. We examined the effect of administering a DNA plasmid encoding IL-12 on the lupus-like disease of MRL/MP-lpr/lpr (MRL/lpr) mice. Treatments were delivered intramuscularly every 4 weeks, starting at 4 weeks of age. This intervention significantly inhibited the accumulation of CD4(-)CD8(-)T cells, and reduced lymphadenopathy and splenomegaly. A significant decrease in serum IgG anti-DNA autoantibody titers was observed, and plasmid IL-12 therapy was also associated with a reduction in the proteinuria and glomerulonephritis characteristic of this disease. Serum IFN-gamma level was increased by inoculating IL-12 encoding plasmid, suggesting that the cytokine balance was skewed towards Th(1). The clinical implications of this suppression of autoimmune disease are also discussed.
系统性红斑狼疮（SLE）的特征是免疫异常，这可通过Th(2)细胞因子的过度产生来解释，如自身抗体产生和多克隆B细胞活化。我们研究了给予编码IL-12的DNA质粒对MRL/MP-lpr/lpr（MRL/lpr）小鼠狼疮样疾病的影响。从4周龄开始，每4周进行一次肌肉注射治疗。这种干预显著抑制了CD4(-)CD8(-)T细胞的积累，并减轻了淋巴结病和脾肿大。观察到血清IgG抗DNA自身抗体滴度显著降低，并且质粒IL-12治疗还与该疾病特征性的蛋白尿和肾小球肾炎的减轻有关。接种编码IL-12的质粒可提高血清IFN-γ水平，表明细胞因子平衡偏向Th(1)。本文还讨论了这种自身免疫性疾病抑制的临床意义。
