IL-4 plays a crucial role in regulating oxidative damage in the liver during schistosomiasis
IL-4 plays a crucial role in regulating oxidative damage in the liver during schistosomiasis
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DOI：
10.4049/jimmunol.166.3.1903
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发表时间：
2001-02-01
影响因子：
4.4
通讯作者：
Pearce, EJ
中科院分区：
文献类型：
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作者：
La Flamme, AC;Patton, EA;Pearce, EJ
肝肿大和肝细胞增殖，在感染寄生蠕虫曼氏血吸虫的野生型（WT）小鼠中的正常反应，被发现在感染IL-4（-/-）小鼠中严重受损。与WT小鼠相比，在肝脏中检测到O-2（-），NO和更高活性的ONOO-水平增加，并由从感染IL-4（-/-）小鼠的肝脏肉芽肿中分离的病变细胞产生。同时，肝脏中的抗氧化剂防御，特别是过氧化氢酶水平，在这些动物的感染过程中急剧下降。这与感染的WT小鼠的情况形成对比，其中过氧化氢酶水平与正常小鼠一样高。因此，感染IL-4（-/-）动物肝脏中活性氧和氮中间体的实际水平可能显著高于感染WT小鼠肝脏中的水平。为了确定这些变化是否导致了IL-4（-/-）动物感染的更严重疾病的发展，我们用尿酸（一种有效的ONOO-清除剂）治疗感染的IL-4（-/-）小鼠。这导致肝细胞增殖显著增加，发病率降低，生存期延长。综上所述，这些数据表明，IL-4在血吸虫病期间通过控制肝脏中活性氧和氮中间产物的产生的严格调节而发挥保护作用。
Liver enlargement and hepatocyte proliferation, normal responses in wild-type (WT) mice infected with the parasitic helminth Schistosoma mansoni, were found to be severely impaired in infected IL-4(-/-) mice. Compared with WT mice, increased levels of O-2(-), NO, and the more highly reactive ONOO- were detected in the liver and produced by lesional cells isolated from liver granulomas of infected IL-4(-/-) mice. Concurrently, antioxidant defenses in the liver, specifically catalase levels, diminished dramatically during the course of infection in these animals. This contrasted to the situation in infected WT mice, where catalase levels remained as high as those in normal mice. Actual levels of reactive oxygen and nitrogen intermediates in the livers of infected IL-4(-/-) animals are thus likely to be considerably higher than those in the livers of infected WT mice. To determine whether these changes contributed to the development of the more severe disease that characterizes infection in the IL-4(-/-) animals, we treated infected IL-4(-/-) mice with uric acid, a potent scavenger of ONOO-. This resulted in significantly increased hepatocyte proliferation, decreased morbidity, and prolonged survival. Taken together, these data indicate that IL-4 is playing a protective role during schistosomiasis by controlling the tight regulation of the generation of reactive oxygen and nitrogen intermediates in the liver.