Polyhexamethyleneguanidine phosphate induces severe lung inflammation, fibrosis, and thymic atrophy.
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.
Inhalation Toxicology Center, Jeonbuk Department of Non-human Primate, Korea Institute of Toxicology, Jeongeup-si, Jeollabukdo 580-185, Republic of Korea.
Jeong Ah
JA
Song
Inhalation Toxicology Center, Jeonbuk Department of Non-human Primate, Korea Institute of Toxicology, Jeongeup-si, Jeollabukdo 580-185, Republic of Korea.
Hyun-Ju
HJ
Park
Toxicopathology Center, Non-human Primate Center, Jeonbuk Department of Non-human Primate, Korea Institute of Toxicology, Jeongeup-si, Jeollabukdo 580-185, Republic of Korea.
Mi-Jin
MJ
Yang
Analytical Center, Korea Institute of Toxicology, Daejeon 305-343, Republic of Korea.
Kyung Jin
KJ
Jung
Inhalation Toxicology Center, Jeonbuk Department of Non-human Primate, Korea Institute of Toxicology, Jeongeup-si, Jeollabukdo 580-185, Republic of Korea.
Hyo-Seon
HS
Yang
Division of Toxicological Research, Korea Institute of Toxicology, Daejeon 305-343, Republic of Korea.
Chang-Woo
CW
Song
Inhalation Toxicology Center, Jeonbuk Department of Non-human Primate, Korea Institute of Toxicology, Jeongeup-si, Jeollabukdo 580-185, Republic of Korea. Electronic address: khlee@kitox.re.kr.
Kyuhong
K
Lee
D000818:Animals; D001284:Atrophy / Q000139:chemically induced; D001835:Body Weight / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006146:Guanidines / Q000633:toxicity*; D008297:Male; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D011014:Pneumonia / Q000139:chemically induced* / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000473:pathology; D013950:Thymus Gland / Q000187:drug effects* / Q000473:pathology
D016207:Cytokines; D006146:Guanidines; C060540:polyhexamethyleneguanidine
Humidifier disinfectant; Lung fibrosis; Polyhexamethyleneguanidine phosphate; Pulmonary inflammation