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

Abstract

Background/aimMelatonin 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. MethodsWe 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. ResultsOne 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. ConclusionsPro-inflammatory responses to O3 exposure in the preceding 2 weeks partly resulted from the depletion of endogenous melatonin by O3.