HIV and paraquat poisoning: fighting fire with fire?

HIV and paraquat poisoning: fighting fire with fire? HIV和百草枯中毒:以毒攻毒? first-author †E-mail:luyuanqiang@zju.edu.cn †E-mail:luyuanqiang@zju.edu.cn luyuanqiang@zju.edu.cn Department of Emergency Medicine, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China Department of Emergency Medicine, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China Though the cases of HIV patients with paraquat (PQ) poisoning are rare, we still found the common features. These recovered HIV patients tended to result in much less lung injury, and had low CD4 + T lymphocyte levels due to HIV infection, which meant they were under the immunosuppressive condition during treatment. This may be conducive to relieve the acute inflammation and lung fibrosis induced by PQ. Thus, we consider the immunosuppressive therapy for PQ poisoning to be appropriate. However, the drugs used currently may be not optimal for toxic patient. As next step, we will add the CD4 + T lymphocyte-targeted immunosuppressive drug to treat PQ poisoning patients. 回顾性分析PubMed收录的仅有3例合并有HIV的急性百草枯中毒患者的救治经过及预后.探索急性百草枯中毒新的免疫治疗.提出采用CD4 + T淋巴细胞作为急性百草枯中毒的免疫治疗精准靶点,可能改善预后,但需要进一步研究和临床实践. Paraquat Human immunodeficiency virus Immunosuppressive therapy 百草枯 艾滋病病毒 免疫抑制治疗 Ingestion by humans of paraquat (PQ), a high-efficiency herbicide, can cause extremely high mortality (60%–70%), since it undergoes cellular redox cycling, leads directly to cell damage and triggers uncontrollable inflammatory responses (Gunnell et al., 2007 2007 ). Once PQ poisoning has occurred, the immune cells of different lineages are activated as major drivers of fibrosis (Fig. 1 1 ). Secondary lung fibrosis is the major cause of death. Because of variable amounts of PQ exposure and individual differences, the outcome of present treatments such as haemoperfusion (HP), antioxidants, and immunosuppressive therapy is not stable and reliable (Zhang et al., 2012 2012 ; Shao et al., 2015 2015 ; Zhao et al., 2015 2015 ; Wang et al., 2017 2017 ). Some key questions need to be solved to improve clinical outcomes following PQ poisoning. We need to select or develop appropriate drugs based on the pathogenic mechanisms and characteristics of PQ. Thus, finding a suitable therapeutic target for PQ detoxification is a critical step. It is known that a loss of CD4 + T lymphocytes is the immune compromise caused by the human immunodeficiency virus (HIV). Only three cases of HIV patients with PQ poisoning are listed in PubMed (Ragoucy-Sengler and Pileire, 1996 1996 ; Shang and Lu, 2015 2015 ; Tsai et al., 2016 2016 ). Fortunately, they all had excellent outcomes. The first case was reported by Ragoucy-Sengler and Pileire ( 1996 1996 ). This HIV-infected patient (with a serum concentration of 1.3 µg/ml PQ, five hours after exposure) survived after receiving lavage and diuresis, in spite of clinical and biological prognoses of death. Our team reported the second case of a 34-year-old man who had HIV infection and severe PQ poisoning (Shang and Lu, 2015 2015 ). He survived with a good outcome despite a usually fatal serum concentration of PQ (2.17 µg/ml, ten hours after exposure) after receiving immunosuppressive therapy and HP. The latest case, published in 2016, involved an HIV patient with PQ poisoning (3.0 µg/ml, three hours after the exposure) who surprisingly survived without treatment (Tsai et al., 2016 2016 ). Though cases of HIV patients with PQ poisoning are rare, we found common features among these three cases. The recovered HIV patients tended to suffer much less lung injury than the general PQ-poisoned patients. In addition, they all had low CD4 + T lymphocyte levels due to HIV infection (Ragoucy-Sengler and Pileire, 1996 1996 ; Shang and Lu, 2015 2015 ; Tsai et al., 2016 2016 ). These low counts of CD4 + T lymphocytes confirmed that the patients were in an immunosuppressed condition, which may be conducive to relieving the acute inflammation and lung fibrosis induced by PQ. The HIV-infected status appears to give a protective effect in PQ-poisoned patients. For this reason, immunosuppressive therapy for PQ poisoning seems to be appropriate. CD4 + T lymphocytes might be a suitable target for immunosuppressive therapy (Fig. 1 1 ). EMT: epithelial-mesenchymal transition; HIV: human immunodeficiency virus; IL: interleukin; PQ: paraquat; ROS: reactive oxygen species Consequently, we suppose the immunosuppressive drugs currently used for PQ detoxification are not optimal. Our next research step is to treat PQ-poisoned patients with CD4 + T lymphocyte-targeted drugs and observe their effects. These drugs, including cyclosprone A, FK506 (tacrolimus), mycophenolate mofetil (MMF), muromonab CD3 (ortholone), and anti-thymocyte/anti-lymphocyte globulin (ATG/ALG), are commonly used in the treatment of allograft rejection. In the long term, the functional inactivation of a donor organ after transplantation is also a process of inflammation and fibrosis, in which CD4 + T cells play a key role (Hügle, 2011 2011 ). Therefore, the proposed use of CD4 + T lymphocytes as a target to guide immunosuppressive therapy to improve the prognosis of PQ-poisoned patients could be feasible. All inferences are uncertain, but science is derived from hypothesis. Herein, we share our ideas with peers, in the hope that we may receive some pertinent suggestions for future work. Controversy 1 1. The first debate refers to the fact that the treatments used in these three cases were different. At present, there is no effective treatment for pulmonary fibrosis caused by PQ, and the clinical treatment strategy is yet to be agreed. Although the three cases in this essay had various treatments, my conclusion and inference were not affected. In particular, the two cured patients who did not receive immunosuppressive therapy demonstrated well the importance of the immune mechanism in PQ poisoning. 2. The second controversy surrounds whether the observed low CD4 + T cell counts were due to HIV-1 disease progression or to a PQ poisoning effect. I would like to clarify that this short essay inferred only that CD4 + T cells could be a target of PQ treatment. The low CD4 + T cell counts in the three cases were caused by HIV infection or immunosuppressive treatment, indicating that the patients who survived were all in an immunosuppressive condition. Clinically, the cause of the low level of CD4 + T cells is not a key point. References D Gunnell , M Eddleston , MR Phillips , 等 . 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Evaluation of efficacy of resin hemoperfusion in patients with acute 2,4-dinitrophenol poisoning by dynamic monitoring of plasma toxin concentration Compliance with ethics guidelines Yuan-qiang LU declares that he has no conflict of interest. This article does not contain any studies with human or animal subjects performed by the author. 10.1631/jzus.B1700567 Project supported by the Science and Technology Department of Zhejiang Province for Beneficial Technology Research of Social Development (No. 2015C33146) and the Key Discipline Construction of Zhejiang Province for Traditional Chinese Medicine (No. 2017-XK-A36), China 2017-11-15 2018-01-25 2022-01-05 Copyright © Zhejiang University and Springer-Verlag GmbH Germany, part of Springer Nature 2018 2018 Journal of Zhejiang University-SCIENCE B (Biomedicine and Biotechnology) 02 19