The impact of a new immunomodulator oxo-quinoline-3-carboxamide on the progression of experimental lupus
The impact of a new immunomodulator oxo-quinoline-3-carboxamide on the progression of experimental lupus
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DOI：
10.1016/j.intimp.2004.07.009
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发表时间：
2004-11-01
影响因子：
5.6
通讯作者：
Tarkowski, A
中科院分区：
文献类型：
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作者：
Carlsten, H;Jonsson, C;Tarkowski, A
用新开发的免疫调节剂氧喹啉-3-甲酰胺(ABR-25757)对自身免疫性狼疮易感的MRL lpr/lpr小鼠进行口服治疗。在一组实验中，在10周大时，在临床上明显的疾病开始之前，在另一组实验中，在已确定的狼疮疾病发展之后的15周，开始治疗。即使当ABR-25757以最低测试剂量(7.5mug/只/周)给15周龄狼疮小鼠时，也获得了有益的治疗效果。ABR-25757在延年益寿和肾小球肾炎的发展方面的作用显著，并可与强大的免疫调节剂LS-2616相媲美。无论在体内还是体外，给予ABR-25757都没有显著改变T细胞的反应。此外，它只略微抑制B细胞的反应，以免疫球蛋白分泌细胞的频率衡量。同样，该化合物不影响初级(骨髓)或次级(脾)淋巴组织中的总白细胞含量。相比之下，ABR-25757治疗上调了促炎转录因子NF-kappaB和AP-1的表达。这些结果提示：(A)ABR-25757在实验性狼疮的治疗中具有潜在的治疗作用；(B)该治疗作用是通过免疫偏离而不是通过免疫抑制来实现的。(C)2004爱思唯尔B.V.保留所有权利。
Autoimmune, lupus-prone MRL lpr/lpr mice were treated orally with oxo-quinoline-3-carboxamide (ABR-25757), a newly developed immunomodulator. Treatment was initiated in one set of experiment at the age of 10 weeks, before the onset of clinically apparent disease, and in another set at 15 weeks, after the development of established lupus disease. Beneficial therapeutic effects were obtained even when ABR-25757 was administered at the lowest dose tested (7.5 mug/mouse/week) to 15 weeks old mice with established lupus disease. The effects of ABR-25757 on longevity, as well as on development of glomerulonephritis were pronounced and comparable with those of LS-2616, a potent immunomodulator. Administration of ABR-25757 did not significantly alter T cell responses in vivo nor in vitro. In addition, it only marginally suppressed B cell responses measured as frequencies of immunoglobulin secreting cells. By the same token this compound did not affect overall leukocyte content in primary (bone marrow) or secondary (spleen) lymphoid tissues. In contrast, treatment with ABR-25757 up regulated expression of pro-inflammatory transcription factors NF-kappaB and AP-1. These results suggest (a) a potential therapeutic role of ABR-25757 in the treatment of experimental lupus and (b) that the effect of the treatment is mediated by immunodeviation rather than by immunosuppression. (C) 2004 Elsevier B.V. All rights reserved.