Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 76100, Israel.
Department of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona 76100, Israel.
Toxins (Basel). 2017 Oct 3;9(10):311. doi: 10.3390/toxins9100311.
Ricin, a plant-derived toxin originating from the seeds of Ricinus communis (castor beans), is one of the most lethal toxins known, particularly if inhaled. Ricin is considered a potential biological threat agent due to its high availability and ease of production. The clinical manifestation of pulmonary ricin intoxication in animal models is closely related to acute respiratory distress syndrome (ARDS), which involves pulmonary proinflammatory cytokine upregulation, massive neutrophil infiltration and severe edema. Currently, the only post-exposure measure that is effective against pulmonary ricinosis at clinically relevant time-points following intoxication in pre-clinical studies is passive immunization with anti-ricin neutralizing antibodies. The efficacy of this antitoxin treatment depends on antibody affinity and the time of treatment initiation within a limited therapeutic time window. Small-molecule compounds that interfere directly with the toxin or inhibit its intracellular trafficking may also be beneficial against ricinosis. Another approach relies on the co-administration of antitoxin antibodies with immunomodulatory drugs, thereby neutralizing the toxin while attenuating lung injury. Immunomodulators and other pharmacological-based treatment options should be tailored according to the particular pathogenesis pathways of pulmonary ricinosis. This review focuses on the current treatment options for pulmonary ricin intoxication using anti-ricin antibodies, disease-modifying countermeasures, anti-ricin small molecules and their various combinations.
蓖麻毒素是一种源自大戟科植物蓖麻（巴豆）种子的植物源性毒素，是已知最致命的毒素之一，尤其是吸入时。由于其高可用性和易于生产，蓖麻毒素被认为是一种潜在的生物威胁剂。动物模型中肺蓖麻中毒的临床表现与急性呼吸窘迫综合征（ARDS）密切相关，涉及肺促炎细胞因子上调、大量中性粒细胞浸润和严重水肿。目前，在临床前研究中，在中毒后临床相关时间点，唯一针对肺 ricinosis 有效的暴露后措施是用抗蓖麻毒素中和抗体进行被动免疫。这种抗毒素治疗的效果取决于抗体亲和力和在有限治疗时间窗内开始治疗的时间。直接干扰毒素或抑制其细胞内运输的小分子化合物也可能对 ricinosis 有益。另一种方法依赖于将抗毒素抗体与免疫调节剂联合给药，从而在中和毒素的同时减轻肺损伤。免疫调节剂和其他基于药理学的治疗选择应根据肺 ricinosis 的特定发病机制途径进行定制。这篇综述重点介绍了使用抗蓖麻毒素抗体、疾病修饰对策、抗蓖麻毒素小分子及其各种组合治疗肺蓖麻中毒的当前治疗选择。
