Endogenous melatonin mediation of systemic inflammatory responses to ozone exposure in healthy adults.
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.
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- Young Adult
- Ozone
- Middle Aged
- Melatonin
- Humans
- Female
- Environmental Sciences
- Cohort Studies
- Air Pollution
- Air Pollutants
Citation
Published In
DOI
EISSN
ISSN
Publication Date
Volume
Start / End Page
Related Subject Headings
- Young Adult
- Ozone
- Middle Aged
- Melatonin
- Humans
- Female
- Environmental Sciences
- Cohort Studies
- Air Pollution
- Air Pollutants