themselves, they are also likely surrogates for other causal species we did not measure that are emitted from the same (traffic) sources. We found little evidence that tracer variables for SOAs and related components (WSOC and organic acids) were associated with the circulating biomarkers in the expected direction. We have no explanation for the negative regression coefficients for organic acids with biomarkers. Although most of the SOAs are expected to be in larger PM > 0.25 µm, the present results are consistent with our finding of few biomarker associations with PM2.5 secondary OC or accumulation mode particle mass (PM0.25–2.5) in an earlier pub­ lication (Delfino et al. 2009). In that study, regression coefficients were also negative for IL6­ in some models with PM 0.25–2.5 and with secondary OC. We speculate that components in outdoor SOAs estimated by our methods (e.g., organic acids), are mostly water solu­ ble and highly oxygenated, and dissolve after deposition on the airway epithelium and then quickly react with extracellular macromole­ cules and cell membrane constituents. Thus, these PM components may not directly inter­ act with the vasculature, although it has been hypothesized that inhaled particles lead to air­ way inflammatory responses and subsequent release of activated leukocytes and cytokines into the circulation (Mills et al. 2009). An important limitation of our characteriza­ tion of SOAs is that WSOCs and organic acids do not completely characterize the SOA fraction of PM, part of which may come from the pho­ tochemical oxidation of low­volatility vapors to form hydrophilic organic components, but whose chemical identity is largely unknown. These precursor vapors include SVOCs that are largely part of POAs. SVOCs evaporate from the particle phase during the process of atmo­ spheric dilution and subsequently react with oxidant gases to form a significant fraction of SOAs (Robinson et al. 2007). Lipid­ soluble components of PM more closely associated with primary emissions, including PAHs, may become bioavailable after deposition followed by distribution of unmetabolized chemicals to the circulation and to extrapulmonary target sites (Gerde et al. 2001). It is also possible that a small fraction of toxic components is carried via various translocation mechanisms into the circulation on UFPs (Mühlfeld et al. 2008). However, translocation may account for a potentially insignificant amount of the impact of UFPs compared with the high retention of UFPs in the lungs (Möller et al. 2008), which may lead to sustained effects through the gradual transfer of redox­ active compo­ nents to the circulation over many days. Although transition metals are known to be redox active, we found no consistent associations with the biomarkers measured, possibly because of low concentrations of these trace elements in the study areas. Finding positive associations of biomark­ ers with both indoor and outdoor PAHs and hopanes along with the indoor/outdoor ratios of these organic components being close to 1.0 suggests that, even though people spend most of their time indoors, indoor air qual­ ity and PM exposures are strongly influenced by PM of outdoor origin. These findings are consistent with our previous analysis for the first half of this panel showing that CMB­ estimated indoor PM of outdoor origin (par­ ticle number, EC, and primary OC) were associated with the biomarkers to a similar degree as outdoor PM (Delfino et al. 2008). Briefly, the exploratory (datad­riven) find ­ ings for GPx­1 and especially Cu,Zn­SOD are consistent with our previous findings for primary OC and EC (Delfino et al. 2009) and suggest antioxidant enzyme inactivation within erythrocytes by traffic­related pollut ­ ant components, including PAHs, among a subgroup of people. This inactivation is anticipated to increase oxidative stress and thus inflammation. This is potentially impor­ tant because these enzymes likely represent important intermediate end points that have been linked to the risk of developing coronary artery disease in prospective cohort and other studies (FloresM­ateo et al. 2009). Given that these findings were far less clear when includ­ ing the entire 60­subject panel (because a small subgroup of seven subjects had positive associations), these results should be viewed as hypothesis generating and retested in other populations. See Delfino et al. (2009) for further details and discussion concerning potential mechanisms of antioxidant enzyme inactivation versus up­ regulation that may explain group differences. Strengths of the present study lie in expo­ sure measurements in each subject’s com­ munity microenvironment and in repeated biological marker assessments in a wellc­harac ­ terized patient sample. Limitations include the potential for unmeasured temporal confound­ ing. However, we performed a priori adjust­ ment for one of the largest sources of variability in inflammatory mediators that have been doc­ umented in the literature (infections), and we also accounted for temperature and for com­ munity and seasonal variability in exposures. We also acknowledge that the present study does perform multiple comparisons, although we did narrow the number of hypotheses being tested based on prior evidence of associations from the work of others and ourselves. The results of the present study suggest that tracer components of mobile source emis­ sions in PM0.25 are associated with increased systemic inflammation in a potentially sus­ ceptible population of elderly individuals. The measured biomarkers likely represent Environmental Health Perspectives • volume 118 | number 6 | June 2010 Biomarkers and particle components important intermediate end points (systemic inflammation) that have been linked to the risk of cardiovascular diseases in prospective cohort and other studies (Kritchevsky et al. 2005; Pai et al. 2004). The positive relation between air pollution and cytokine bio­ markers may also be indicative of acute risk of adverse cardiovascular outcomes related to vascular dysfunction and atherothrombo­ sis (Mills et al. 2009). We recently reported coherent associations between hourly ambula­ tory systolic and diastolic blood pressure and hourly air pollutant exposures in the present panel cohort, including stronger associations with primary PM2.5 OC compared with sec­ ondary PM2.5 OC (Delfino et al. 2010). We conclude that U.S. EPA–regulated ambient PM2.5 mass measurements may not adequately represent risk to human health because they are uncharacterized by composi­ tion, source, or PM size distribution and are not necessarily representative of personal or local exposure. Confirmatory data are needed in other populations using measurements of organic components across several PM size fractions. Ref Rencs Aderka D. 1996. The potential biological and clinical signifi- cance of the soluble tumor necrosis factor receptors. Cytokine Growth Factor Rev 7:231–240. Araujo JA, Barajas B, Kleinman M, Wang X, Bennett BJ, Gong KW, et al. 2008. 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