Fine particulate matter exposure and systemic inflammation: A potential mediating role of bioactive lipids

Inflammation is a key mechanism underlying the adverse health effects of exposure to fine particulate matter (PM_2.5). Bioactive lipids in the arachidonic acid (ARA) pathway are important in the regulation of inflammation and are reportedly altered by PM_2.5 exposure. Ceramide-1-phosphate (C1P), a class of sphingolipids, is required to initiate ARA metabolism. We examined the role of C1P in the alteration of ARA metabolism after PM_2.5 exposure and explored whether changes in the ARA pathway promoted systemic inflammation based on a panel study involving 112 older adults in Beijing, China. Ambient PM_2.5 levels were continuously monitored at a fixed station from 2013 to 2015. Serum cytokine levels were measured to assess systemic inflammation. Multiple bioactive lipids in the ARA pathway and three subtypes of C1P were quantified in blood samples. Mediation analyses were performed to test the hypotheses. We observed that PM_2.5 exposure was positively associated with inflammatory cytokines and the three subtypes of C1P. Mediation analyses showed that C1P significantly mediated the associations of ARA and 5, 6-dihydroxyeicosatrienoic acid (5, 6-DHET), an ARA metabolite, with PM_2.5 exposure. ARA, 5, 6-DHET, and leukotriene B4 mediated systemic inflammatory response to PM_2.5 exposure. For example, C1P C16:0 (a subtype of C1P) mediated a 12.9 % (95 % confidence interval: 3.7 %, 32.5 %) increase in ARA associated with 3-day moving average PM_2.5 exposure, and ARA mediated a 27.1 % (7.8 %, 61.2 %) change in interleukin-8 associated with 7-day moving average PM_2.5 exposure. Our study indicates that bioactive lipids in the ARA and sphingolipid metabolic pathways may mediate systemic inflammation after PM_2.5 exposure.