Song Jeong Ah, Park Hyun-Ju, Yang Mi-Jin, Jung Kyung Jin, Yang Hyo-Seon, Song Chang-Woo, Lee Kyuhong
Inhalation Toxicology Center, Jeonbuk Department of Non-human Primate, Korea Institute of Toxicology, Jeongeup-si, Jeollabukdo 580-185, Republic of Korea.
Toxicopathology Center, Non-human Primate Center, Jeonbuk Department of Non-human Primate, Korea Institute of Toxicology, Jeongeup-si, Jeollabukdo 580-185, Republic of Korea.
Food Chem Toxicol. 2014 Jul;69:267-75. doi: 10.1016/j.fct.2014.04.027. Epub 2014 Apr 22.
Polyhexamethyleneguanidine phosphate (PHMG-P) has been widely used as a disinfectant because of its strong bactericidal activity and low toxicity. However, in 2011, the Korea Centers for Disease Control and Prevention and the Ministry of Health and Welfare reported that a suspicious outbreak of pulmonary disease might have originated from humidifier disinfectants. The purpose of this study was to assess the toxicity of PHMG-P following direct exposure to the lung. PHMG-P (0.3, 0.9, or 1.5 mg/kg) was instilled into the lungs of mice. The levels of proinflammatory markers and fibrotic markers were quantified in lung tissues and flow cytometry was used to evaluate T cell distribution in the thymus. Administration of PHMG-P induced proinflammatory cytokines elevation and infiltration of immune cells into the lungs. Histopathological analysis revealed a dose-dependent exacerbation of both inflammation and pulmonary fibrosis on day 14. PHMG-P also decreased the total cell number and the CD4(+)/CD8(+) cell ratio in the thymus, with the histopathological examination indicating severe reduction of cortex and medulla. The mRNA levels of biomarkers associated with T cell development also decreased markedly. These findings suggest that exposure of lung tissue to PHMG-P leads to pulmonary inflammation and fibrosis as well as thymic atrophy.
聚六亚甲基胍磷酸盐（PHMG-P）因其强大的杀菌活性和低毒性而被广泛用作消毒剂。然而，2011年，韩国疾病控制与预防中心以及卫生与福利部报告称，一起可疑的肺部疾病暴发可能源于加湿器消毒剂。本研究的目的是评估直接暴露于肺部后PHMG-P的毒性。将PHMG-P（0.3、0.9或1.5毫克/千克）注入小鼠肺部。对肺组织中的促炎标志物和纤维化标志物水平进行定量，并使用流式细胞术评估胸腺中的T细胞分布。给予PHMG-P可诱导促炎细胞因子升高以及免疫细胞浸润到肺部。组织病理学分析显示，在第14天炎症和肺纤维化呈剂量依赖性加重。PHMG-P还降低了胸腺中的总细胞数和CD4(+)/CD8(+)细胞比率，组织病理学检查表明皮质和髓质严重减少。与T细胞发育相关的生物标志物的mRNA水平也显著降低。这些发现表明，肺组织暴露于PHMG-P会导致肺部炎症、纤维化以及胸腺萎缩。
