Endogenous melatonin mediation of systemic inflammatory responses to ozone exposure in healthy adults.

Journal Article (Journal Article)


Melatonin is a free radical scavenger and an anti-inflammatory biomolecule. Air pollution exposure has been associated with increased inflammatory responses. We hypothesize that endogenous melatonin plays a role in inflammatory responses to air pollution exposure.


We tested this hypothesis in a cohort of 53 healthy adults (22-52 years old, 16 women), none of whom were on melatonin supplementation. Early morning urine and fasting blood were collected from each participant longitudinally up to three times. We analyzed urinary 6-sulfatoxymelatonin (aMT6s), as a surrogate of circulating melatonin, and pro- and anti-inflammatory cytokines in the plasma samples. Indoor and outdoor air pollutants were measured and combined with participants' time-activity patterns to calculate personal exposure to O3 , PM2.5 , NO2 , and SO2 averaged over 12-hour, 24-hour, 1-week, and 2-week periods prior to biospecimen collection, respectively. Linear mixed-effects models were used to examine the relationships among urinary aMT6s, personal pollutant exposure, and plasma cytokines. A mediation analysis was conducted to examine the role of aMT6s in the relationships between pollutant exposures and inflammatory cytokines.


One interquartile range (4.2 ppb) increase in 2-week O3 exposure was associated with a -26.2% (95% CI: -43.9% to -2.8%) decrease in aMT6s. Within the range of endogenous aMT6s concentrations (0.5-53.0 ng/ng creatinine) across the participants, increased aMT6s was associated with decreased pro-inflammatory cytokines including IL-1β, IL-8, IL-17A, IFN-γ, and TNF-α. These cytokines were significantly and positively associated with 2-week average O3 exposure. Furthermore, 7.4% to 17.4% of the O3 -cytokine associations were mediated by aMT6s. We did not find similar effects for the other pollutants.


Pro-inflammatory responses to O3 exposure in the preceding 2 weeks partly resulted from the depletion of endogenous melatonin by O3 .

Full Text

Duke Authors

Cited Authors

  • He, L; Hu, X; Gong, J; Day, D; Xiang, J; Mo, J; Zhang, Y; Zhang, J

Published Date

  • December 2020

Published In

Volume / Issue

  • 749 /

Start / End Page

  • 141301 -

PubMed ID

  • 32829269

Electronic International Standard Serial Number (EISSN)

  • 1879-1026

International Standard Serial Number (ISSN)

  • 0048-9697

Digital Object Identifier (DOI)

  • 10.1016/j.scitotenv.2020.141301


  • eng