In the population-based CoLaus study, short-term exposure to PM10 was associated with circulating levels of IL-1β, IL-6 and TNF-α, but not of hs-CRP. Our results are consistent with findings by Ruckerl et al., who showed no association of PM10 with hs-CRP, but a significant positive association of particle number concentration with IL-6 levels in 1003 myocardial infarction (MI) survivors . In several small-sized studies, similar associations were found [24–26]. Furthermore, our results are in line with experimental data. Van Eeden et al.  showed that human alveolar macrophages produce TNF-α in a dose-dependent manner when exposed to atmospheric particles. Kido et al.  found the lung to be a major source of systemic circulating IL-6 levels in mice exposed to ambient PM. Our study is the first large scale population-based study to show significant positive associations of short-term exposure to PM10 with circulating IL-1β, IL-6 and TNF-α levels, which substantially increases the external validity of previous findings. The relevance of these results is emphasized by the fact that IL-6 plays a central role in the inflammatory response in the context of cardiovascular disease .
Systemic inflammation is known to be associated with cardiovascular morbidity and mortality . Indeed, a number of epidemiological and experimental studies have shown that circulating markers of systemic inflammation and haemostasis are closely associated with the development of fatal and non-fatal MI [28–32]. Inflammation is likely to interfere directly with the blood coagulation pathways leading to hypercoagulation states , as well as to increase the probability for a plaque rupture leading to acute coronary events by accentuating atherosclerotic plaque vulnerability . These findings, together with the observation that short-term exposure to higher PM10 levels are associated with the risk of myocardial infarction and acute ischemic stroke , suggest that air pollution-induced systemic inflammation may increase cardiovascular risk .
Many hypotheses have been proposed to explain the pathophysiological mechanism underlying the link between PM inhalation and systemic inflammation. Exposure of the pulmonary bronchial tree to PM may induce a local inflammatory reaction with the production of specific cytokines from neutrophils, macrophages and T cells . In vitro studies have shown that human alveolar macrophages exposed to PM10 release numerous inflammatory cytokines, including IL-6 and TNF-α [6, 7, 24]. The diffusion of these cytokines in the systemic circulation induces a generalized reaction leading to the inflammation cascade . Recently, a second hypothesis has been proposed, suggesting that inhaled PM and especially PM2.5 directly penetrate into the vascular tree where they interact with endothelial cells and the immune system further activating the inflammation cascade .
We found no association of short-term exposure to PM10 with circulating hs-CRP levels. This is in line with the results of previous population-based studies [20, 21, 23]. The absence of association with hs-CRP might be related to the fact that we only explored short-term exposure, as one study found a positive association of hs-CRP with long-term exposure to PM10. Yet, Hertel at al found short-term exposure to particle number to be associated with hs-CRP in 4000 participants to the population-based Heinz Nixdorf Recall study . CRP production is increased following the hepatic action of IL-6. CRP represents a later marker of inflammation than IL-6, for instance, with a half-life of around 15–19 hours for CRP . This may explain the absence of association with short-term exposure to PM10 in our study.
This study has some limitations which should be acknowledged. This is a cross-sectional analysis using the absolute level of PM10 at a single point in time. Unfortunately, data for PM2.5 was not available in this study. Also, our results only pertain to short-term exposure to PM10. The effects of long-term exposure to PM10 levels could not be assessed because long-term individual-level exposure data are not available. Personal exposures can vary substantially from the levels measured at a central monitoring station. We did not capture differences in long-term exposure due to different exposures to local sources (roads, industrial sources). This is a problem common to large epidemiological studies that, unlike panel studies, cannot equip each subject with personal exposure monitoring devices. To account for variations attributable to spatial differences in participants’ place of residence, we included the zip code as a covariate in the models. PM10 is a complex mixture of chemical compounds the behavior of which strongly depends on the atmospheric conditions. Putard et al. reported that the most important compounds to PM10 mass in four Swiss locations (Bern, Zurich, Basel, and Chaumont) were black carbon, organic matter, mineral dust, ammonium, nitrate and sulphate . The studied population is from a single geographical area, and the findings may not be generalisable to other regions or cities. In addition, results for IL-1β should be interpreted with caution because 38 % of IL-1β was below the detection limit of the assay. More sensitive assays are therefore needed to reduce the proportion of undetectable values for IL-1β and to provide better estimates of the association of PM10 with circulating IL-1β levels.