tetano
Editor, Senior Moderator
J Hazard Mater
. 2026 Mar 1:506:141632.
doi: 10.1016/j.jhazmat.2026.141632. Online ahead of print.
Unveiling a macrophage-driven inflammatory dysregulation: NF-κB-mediated hyperinflammation links 6PPD-Q exposure to viral immunopathology
Xia-Wen Qiu[SUP] 1 [/SUP], Jiajun Chen[SUP] 2 [/SUP], Jiayan Wang[SUP] 3 [/SUP], Yujie Li[SUP] 4 [/SUP], Xiaoyan Qi[SUP] 1 [/SUP], Xianchang Zeng[SUP] 5 [/SUP], Huajun Feng[SUP] 6 [/SUP], Xianghui Kong[SUP] 7 [/SUP]
Affiliations
Respiratory viral infections contribute substantially to global disease burden and mortality. N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-Q) has garnered significant attention due to its marked ecotoxicity. However, it remains unclear how this prevalent environmental pollutant impacts host immune defense against respiratory viral infections. This study established a murine model involving 14-day consecutive intranasal administration of environmentally relevant doses of 6PPD-Q coupled with intranasal instillation of influenza A virus (IAV) or tail vein injection of vesicular stomatitis virus (VSV). Our findings revealed that mice pre-exposed to 6PPD-Q exhibited higher mortality during viral infection. Notably, 6PPD-Q exposure resulted in extensive viral dissemination, severe pulmonary pathology, and markedly dysregulated inflammation, characterized by excessive increases in IL-6, TNF-α, IL-1β, and IL-10. Immune profiling demonstrated that 6PPD-Q exposure induced the selective accumulation of neutrophils, monocytes, and monocyte-derived macrophages (MDMs) in the lungs during IAV infection. Interestingly, macrophage depletion unequivocally abolished the differences of survival, viral loads, and cytokine levels between the vehicle- and 6PPD-Q-treated mice. Mechanistically, 6PPD-Q activated NF-κB signaling in pulmonary MDMs, driving excessive inflammatory responses. Our findings confirm that 6PPD-Q significantly increases host susceptibility to viral pneumonia. This underscores the critical significance of environmental health management in the prevention and control of respiratory infectious diseases.
Keywords: 6PPD-quinone; Immune dysregulation; Macrophage; Respiratory exposure; Virus infection.
. 2026 Mar 1:506:141632.
doi: 10.1016/j.jhazmat.2026.141632. Online ahead of print.
Unveiling a macrophage-driven inflammatory dysregulation: NF-κB-mediated hyperinflammation links 6PPD-Q exposure to viral immunopathology
Xia-Wen Qiu[SUP] 1 [/SUP], Jiajun Chen[SUP] 2 [/SUP], Jiayan Wang[SUP] 3 [/SUP], Yujie Li[SUP] 4 [/SUP], Xiaoyan Qi[SUP] 1 [/SUP], Xianchang Zeng[SUP] 5 [/SUP], Huajun Feng[SUP] 6 [/SUP], Xianghui Kong[SUP] 7 [/SUP]
Affiliations
- PMID: 41785783
- DOI: 10.1016/j.jhazmat.2026.141632
Respiratory viral infections contribute substantially to global disease burden and mortality. N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-Q) has garnered significant attention due to its marked ecotoxicity. However, it remains unclear how this prevalent environmental pollutant impacts host immune defense against respiratory viral infections. This study established a murine model involving 14-day consecutive intranasal administration of environmentally relevant doses of 6PPD-Q coupled with intranasal instillation of influenza A virus (IAV) or tail vein injection of vesicular stomatitis virus (VSV). Our findings revealed that mice pre-exposed to 6PPD-Q exhibited higher mortality during viral infection. Notably, 6PPD-Q exposure resulted in extensive viral dissemination, severe pulmonary pathology, and markedly dysregulated inflammation, characterized by excessive increases in IL-6, TNF-α, IL-1β, and IL-10. Immune profiling demonstrated that 6PPD-Q exposure induced the selective accumulation of neutrophils, monocytes, and monocyte-derived macrophages (MDMs) in the lungs during IAV infection. Interestingly, macrophage depletion unequivocally abolished the differences of survival, viral loads, and cytokine levels between the vehicle- and 6PPD-Q-treated mice. Mechanistically, 6PPD-Q activated NF-κB signaling in pulmonary MDMs, driving excessive inflammatory responses. Our findings confirm that 6PPD-Q significantly increases host susceptibility to viral pneumonia. This underscores the critical significance of environmental health management in the prevention and control of respiratory infectious diseases.
Keywords: 6PPD-quinone; Immune dysregulation; Macrophage; Respiratory exposure; Virus infection.