TUMOR-NECROSIS-FACTOR-ALPHA IN MURINE SYSTEMIC LUPUS-ERYTHEMATOSUS DISEASE-MODELS - IMPLICATIONS FOR GENETIC PREDISPOSITION AND IMMUNE REGULATION
TUMOR-NECROSIS-FACTOR-ALPHA IN MURINE SYSTEMIC LUPUS-ERYTHEMATOSUS DISEASE-MODELS - IMPLICATIONS FOR GENETIC PREDISPOSITION AND IMMUNE REGULATION
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DOI：
10.1016/1043-4666(91)90481-r
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发表时间：
1991-11-01
期刊：
影响因子：
3.8
通讯作者：
STALL, AM
中科院分区：
文献类型：
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作者：
JACOB, CO;HWANG, F;STALL, AM
重组肿瘤坏死因子α (TNF-α)在新西兰黑×新西兰白（NZB × NZW）F1中显著延迟狼疮样肾炎的发展，在MRL-lpr/lpr模型系统中也有较小程度的延迟。TNF-α治疗在2、3或4月龄时开始有效，但如果晚至6.5月龄时开始无效。（NZB × NZW）F1小鼠治疗3个月比持续治疗6个月更有效。抗tnf -α抗体在这些小鼠中没有产生。流动微荧光分析显示，对腹膜、脾脏、淋巴结和胸腺细胞中的B、T或单核细胞群没有重大影响。TNF-α-处理小鼠腹膜巨噬细胞ⅱ类Ia表达降低。体外TNF-α诱导水平与体内TNF-α给药效果之间存在相关性。虽然限制性片段长度多态性可以显示有限的多态性，但使用位于TNF-α 5 '调控区域的扩增（AC）n微卫星，发现了更广泛的等位基因间多态性。在NZW小鼠中发现的AC微卫星等位基因是独特的，与其他狼疮菌株和非自身免疫性菌株不同。这些结果可能对系统性红斑狼疮的发病机制有所启示。
Recombinant tumor necrosis factor alpha (TNF-α) administration significantly delayed the development of lupuslike nephritis in the New Zealand black × New Zealand white (NZB × NZW)F1 and to a lesser extent in the MRL-lpr/lpr model systems. TNF-α treatment was effective when treatment was initiated at 2, 3, or 4 months of age but was ineffective if initiated as late as 6.5 months of age. Treatment of (NZB × NZW)F1 mice for 3 months was more effective than treatment continued for 6 months. Anti-TNF-α antibodies did not develop in these mice. Flow microfluorometry analysis showed no major effects on B, T, or monocyte cell population in cells from the peritoneum, spleen, lymph node, and thymus. A decrease in class II Ia expression on macrophages in the peritoneum of TNF-α-treated mice was noticed. A correlation between the level of TNF-α inducibility in vitro and the effect of TNF-α administration in vivo could be shown. Although a limited polymorphism could be shown by restriction fragment length polymorphism, using an amplified (AC)n microsatellite located in the 5′ regulatory region of TNF-α, a much more extensive interallelic polymorphism was found. The AC microsatellite allele found in NZW mice was unique and different from other lupus strains and nonautoimmune strains. These results have possible implications to the pathogenesis of systemic lupus erythematosus.