Treatment of Paraquat-Induced Lung Injury With an Anti-C5a Antibody: Potential Clinical Application.
Treatment of Paraquat-Induced Lung Injury With an Anti-C5a Antibody: Potential Clinical Application.
复制标题
用抗 C5a 抗体治疗百草枯引起的肺损伤：潜在的临床应用。
DOI：
10.1097/ccm.0000000000002950
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发表时间：
2018-05
影响因子：
8.8
通讯作者：
Zhou Y
中科院分区：
文献类型：
--
作者：
Sun S;Jiang Y;Wang R;Liu C;Liu X;Song N;Guo Y;Guo R;Du L;Jiang S;Li Y;Qiu Z;Zhao G;Zhou Y
文本中提供了补充数字内容。补体激活产物 C5a 在病毒、细菌和毒剂（包括百草枯中毒）引起的全身炎症反应综合征中发挥着关键作用。本研究旨在探讨抗C5a药物干预对百草枯中毒引起的全身炎症反应的有效性。食蟹猴模型及百草枯中毒患者血浆的研究。实验室调查。食蟹猴 (n = 12) 和患者血浆样本 (n = 16)。给予中和抗人C5a抗体（IFX-1）以研究食蟹猴模型中百草枯诱导的全身炎症反应的新治疗策略。此外，通过IFX-1阻断百草枯患者血浆中的C5a活化，以研究抗C5a抗体对炎症细胞活化的阻断作用。在急性肺损伤患者和百草枯中毒灵长类动物模型中发现补体激活失调和随后的细胞因子风暴。 IFX-1 对 C5a 的靶向抑制可显着减轻灵长类动物模型中的全身炎症反应和多器官损伤。此外，阻断患者血浆中的C5a活性完全抑制了正常供体的血液粒细胞上CD11b的激活，这表明IFX-1可以减轻炎症反应的过度激活，对急性肺损伤患者具有临床实用性。抗C5a抗体（例如IFX-1）可用作治疗因化学中毒（例如百草枯）引起的全身炎症反应的患者的有效治疗剂。
Supplemental Digital Content is available in the text. Complement activation product C5a plays a critical role in systemic inflammatory response syndrome induced by viruses, bacteria, and toxic agents including paraquat poisoning. This study is to explore the efficiency of anti-C5a–based intervention on systemic inflammatory responses induced by paraquat poisoning. Study of cynomolgus macaque model and plasma from paraquat-poisoning patients. Laboratory investigation. Cynomolgus macaque (n = 12) and samples of plasma from patients (n = 16). The neutralizing antihuman C5a antibody (IFX-1) was administered to investigate the new treatment strategy for paraquat-induced systemic inflammatory responses in cynomolgus macaque model. In addition, C5a activation in plasma of paraquat patients was blocked by IFX-1 to investigate the blockade role of anti-C5a antibody in activation of inflammatory cells. Dysregulated complement activation and the subsequent cytokine storm were found in patients with acute lung injury and in a primate model of paraquat poisoning. Targeted inhibition of C5a by IFX-1 led to marked alleviation of systemic inflammatory responses and multiple organ damage in the primate model. In addition, blockade of C5a activity in plasma from patients completely inhibited activation of CD11b on blood granulocytes from normal donors, suggesting that IFX-1 may alleviate the excessive activation of inflammatory responses and have clinical utility for patients with acute lung injury. Anti-C5a antibodies such as IFX-1 may be used as effective therapeutics for treatment of those suffering from systemic inflammatory responses induced by chemical poisoning like paraquat.