Concentrated ambient fine particles and not ozone induce a systemic interleukin-6 response in humans

Abstract

Epidemiological studies have established significant associations between ambient pollutants, including fine particulate matter (PM_2.5) and ozone (O₃), and cardiopulmonary morbidity and mortality. One mechanism that has been proposed is a pulmonary/systemic inflammatory response. Although controlled human exposure studies have examined the independent inflammatory responses of PM_2.5 and O₃, no studies have previously examined their joint effects. The study objective was to examine the independent and combined associations between ambient PM_2.5 and O₃ and acute respiratory/inflammatory responses. Using their concentrated ambient particle (CAP) facility for PM_2.5, the authors studied 10 mild asthmatic and 13 nonasthmatic individuals. The 2-h exposures included CAP (range 48–199 μg/m³) and filtered air (FA), with/without O₃ (120 ppb), in a randomized block design. Response measures included pulmonary function and inflammatory indices in induced sputum (interleukin [IL]-6, cytology) and blood (IL-6, tumor necrosis factor [TNF]-α) measured before and after exposures. Three hours post exposure, there was an increase in blood levels of IL-6, but only after CAP alone exposures; the IL-6 increase was associated with increasing PM_2.5 mass concentration (p = .005). Some individuals switched to shallow breathing during CAP+O₃, possibly accounting for an attenuation of the resultant blood IL-6 response. Asthmatic and nonasthmatic responses were similar. There were no adverse changes in pulmonary function or other inflammatory measures. The study demonstrated an acute IL-6 response to PM_2.5, providing evidence to support the epidemiological findings of associations between ambient levels of particles and cardiopulmonary morbidity and mortality.

Keywords::

• Air pollution
• particulate matter
• ozone
• interleukin-6
• inflammation

Acknowledgement

We thank the staff at GOEHU that contributed and Vladimir Lukic for the Figure illustrations.

Declaration of interest

This work was supported by Natural Resources Canada, Health Canada (Toxic Substances Research Initiative), Air Quality Health Effects Research Section Government of Canada, Environment Canada, Ontario Thoracic Society, AllerGen NCE Inc., NIH/NIEHS (P01 ES09825) and US EPA (R832416). Although the research described in this article was funded in part by the US EPA through grant R832416 to Harvard University, it has not been subjected to the Agency’s required peer and policy review and therefore does not necessarily reflect the views of the Agency and no official endorsement should be inferred.