Yen Ju-Shao, Wang I-Kuan, Liang Chih-Chia, Fu Jen-Fen, Hou Yi-Chou, Chang Chih-Chun, Gu Po-Wen, Tsai Kai-Fan, Weng Cheng-Hao, Huang Wen-Hung, Hsu Ching-Wei, Yen Tzung-Hai
Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital Linkou 333, Taiwan.
Department of Nephrology, China Medical University Hospital Taichung 404, Taiwan.
Am J Transl Res. 2021 Oct 15;13(10):11571-11584. eCollection 2021.
Cytokine-mediated inflammation is involved in the pathophysiology of paraquat toxicity. Nevertheless, few human studies have examined fluctuations in circulating cytokine levels. Blood samples were obtained from 21 patients with paraquat poisoning and compared to those of 18 healthy controls. All paraquat patients received a standard detoxification protocol composed of hemoperfusion, pulse therapies of methylprednisolone and cyclophosphamide, followed by dexamethasone therapy. Nonsurvivors not only had higher scores for the severity index of paraquat poisoning (P=0.004) but also presented with higher white blood cell counts (P=0.046) than survivors. Multiplex immunoassays revealed higher circulating levels of interleukin 2 (IL-2), interleukin 9 (IL-9), interleukin 10 (IL-10) and macrophage inflammatory protein-1 beta (MIP-1β) in survivors than in healthy controls. Furthermore, the circulating levels of interleukin 1 beta (IL-1β), IL-2, interleukin 5 (IL-5), interleukin 8 (IL-8), IL-9, IL-10, interleukin 12 (IL-12 p70), interleukin 17A (IL-17A), eotaxin, granulocyte colony-stimulating factor (G-CSF), monocyte chemoattractant protein-1 (MCP-1), interferon gamma-induced protein 10 (IP-10) and MIP-1β were higher in nonsurvivors than in healthy controls. Finally, the circulating levels of IL-1β and MCP-1 were higher in nonsurvivors than in survivors. Therefore, the observation of cytokine-mediated inflammation is in line with the detoxification protocol because glucocorticoids and cyclophosphamide are potent anti-inflammatory agents. Additionally, circulating levels of IL-1β and MCP-1 could serve as promising prognostic markers for patients with paraquat poisoning.
细胞因子介导的炎症参与了百草枯中毒的病理生理过程。然而,很少有人类研究检测循环细胞因子水平的波动情况。从21例百草枯中毒患者中采集血样,并与18例健康对照者的血样进行比较。所有百草枯中毒患者均接受了由血液灌流、甲泼尼龙和环磷酰胺脉冲治疗,随后进行地塞米松治疗组成的标准解毒方案。非幸存者不仅百草枯中毒严重指数得分更高(P = 0.004),而且白细胞计数也高于幸存者(P = 0.046)。多重免疫分析显示,幸存者中白细胞介素2(IL-2)、白细胞介素9(IL-9)、白细胞介素10(IL-10)和巨噬细胞炎性蛋白-1β(MIP-1β)的循环水平高于健康对照者。此外,非幸存者中白细胞介素1β(IL-1β)、IL-2、白细胞介素5(IL-5)、白细胞介素8(IL-8)、IL-9、IL-10、白细胞介素12(IL-12 p70)、白细胞介素17A(IL-17A)、嗜酸性粒细胞趋化因子、粒细胞集落刺激因子(G-CSF)、单核细胞趋化蛋白-1(MCP-1)、干扰素γ诱导蛋白10(IP-10)和MIP-1β的循环水平高于健康对照者。最后,非幸存者中IL-1β和MCP-1的循环水平高于幸存者。因此,对细胞因子介导的炎症的观察与解毒方案一致,因为糖皮质激素和环磷酰胺是有效的抗炎药物。此外,IL-1β和MCP-1的循环水平可作为百草枯中毒患者有前景的预后标志物。