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 (O(3)), 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 O(3), 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 O(3) 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 microg/m(3)) and filtered air (FA), with/without O(3) (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]-alpha) 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+O(3), 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.

FIG 1

Association between CAP mass concentration and blood IL-6 change 3-hrs post for CAP and CAP+O₃ exposures. Individual data are shown for 80 exposures. Data for FA (●) and O₃ (□) are shown separately to the left. A solid regression line is shown for CAP observations (▼) and dashed line for CAP+O₃ observations (◊). There was a significant positive association between PM mass concentration and IL-6 change 3-hrs after for CAP but not for CAP+O₃ exposures, with significant effect modification by ozone. The 3-hr post ΔIL-6= 3-hr IL-6 minus pre-exposure IL-6. Abbreviations: FA, filtered air; CAP, concentrated ambient particle; O₃, ozone; PM, particulate matter.

FIG 2

Association between tidal volume 2-hr percent change and blood IL-6 change post exposure. Individual data are shown. Regression lines are shown by solid lines. Pearson partial correlations coefficients are reported, controlling for repeated measures of CAP_<100 and CAP_≥100. (A–C) CAP+O₃ exposures: 10-min post; 3-hrs post; and 20-hrs post. (D–F) CAP exposures: 10-min post; 3-hrs post; and 20-hr post. There were significant positive associations between tidal volume percent change during CAP+O₃ exposures and IL-6 changes at all three time points after but not for CAP alone exposures. Tidal volume 2-hr %Δ= 100 × [(2-hr minus 0-hr) / 0-hr]. Post ΔIL-6= post IL-6 minus pre-exposure IL-6. Abbreviations: CAP, concentrated ambient particle; O₃, ozone.