TNFα and IL-6 Responses to Particulate Matter in Vitro: Variation According to PM Size, Season, and Polycyclic Aromatic Hydrocarbon and Soil Content

Abstract

Background: Observed seasonal differences in particulate matter (PM) associations with human health may be due to their composition and to toxicity-related seasonal interactions.

Objectives: We assessed seasonality in PM composition and in vitro PM pro-inflammatory potential using multiple PM samples.

Methods: We collected 90 weekly PM10 and PM2.5 samples during the rainy-warm and dry-cold seasons in five urban areas with different pollution sources. The elements, polycyclic aromatic hydrocarbons (PAHs), and endotoxins identified in the samples were subjected to principal component analysis (PCA). We tested the potential of the PM to induce tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6) secretion in cultured human monocytes (THP-1), and we modeled pro-inflammatory responses using the component scores.

Results: PM composition varied by size and by season. PCA identified two main components that varied by season. Combustion-related constituents (e.g., vanadium, benzo[a]pyrene, benzo[a]anthracene) mainly comprised component 1 (C1). Soil-related constituents (e.g., endotoxins, silicon, aluminum) mainly comprised component 2 (C2). PM from the rainy-warm season was high in C2. PM (particularly PM2.5) from the dry-cold season was rich in C1. Elevated levels of cytokine production were associated with PM10 and C2 (rainy-warm season), whereas reduced levels of cytokine production were associated with PM2.5 and C1 (dry-cold season). TNFα secretion was increased following exposure to PM with high (vs. low) C2 content, but TNFα secretion in response to PM was decreased following exposure to samples containing ≥ 0.1% of C1-related PAHs, regardless of C2 content. The results of the IL-6 assays suggested more complex interactions between PM components and particle size.

Conclusions: Variations in PM soil and PAH content underlie seasonal and PM size-related patterns in TNFα secretion. These results suggest that the mixture of components in PM explains some seasonal differences in associations between health outcomes and PM in epidemiologic studies.

Citation: Manzano-León N, Serrano-Lomelin J, Sánchez BN, Quintana-Belmares R, Vega E, Vázquez-López I, Rojas-Bracho L, López-Villegas MT, Vadillo-Ortega F, De Vizcaya-Ruiz A, Rosas Perez I, O'Neill MS, Osornio-Vargas AR. 2016. TNFα and IL-6 responses to particulate matter in vitro: variation according to PM size, season, and polycyclic aromatic hydrocarbon and soil content. Environ Health Perspect 124:406-412; http://dx.doi.org/10.1289/ehp.1409287.

Figure 1

C₁, C₂ component scores plot according to PM size and season. Samples (n = 90) according to season and PM size (groups) are well differentiated in their content of C₁ and C₂. Rainy-warm PM₁₀ had high concentrations of C₂ and moderate concentrations of C₁; dry-cold PM₁₀ presented moderate C₁ concentrations and moderate-high concentrations of C₂; rainy-warm PM_2.5 generally had low concentrations of C₁ and C₂; dry-cold PM_2.5 showed high concentrations of C₁ and low concentrations of C₂. The zeroes on both axes correspond to the mean of all samples, and integer values are based on the component loading of the observation and the standardized value of the original variable, summed over all variables.

Figure 2

Scatter plots presenting ln(cytokine responses) and PM C₁ and C₂ component scores. Patterns of association between TNFα and C₁ and C₂ were observed. (A) Low levels of PM-induced TNFα secretion occurred with very low and very high values of C₁, corresponding to PM_2.5 samples from rainy-warm and dry-cold seasons, respectively. The overall correlation was negative (r = –0.32; p = 0.002). (B) C₂ and TNFα values showed a significant positive correlation (r = 0.65; p < 0.001). (C,D) Highly dispersed low correlation patterns of IL-6 with C₁ (r = –0.36; p = 0.000) and C₂ (r = 0.50; p = 0.000) were shown. Cytokine values after subtracting cytokine levels produced by non-exposed control cells are presented. The zeroes on the x-axis correspond to the mean of all samples, and integer values are based on the observation’s component loading and the standardized value of the original variable, summed over all variables. Abbreviations: C₁, Component 1; C₂, component 2; IL-6, Interleukin 6; TNFα, tumor necrosis factor alpha.

Figure 3

Scatter plot of PM-induced TNFα versus the percentage of PM C₁-related PAHs. (A) The relationship between ln(TNFα) and PM C₁-related PAHs was negative (adjusted R ² = 0.75; probability > F = 0.000). (B) Untransformed data show that TNFα production is markedly reduced when C₁-related PAHs > ~ 0.1% or C₁ + C₂ content is low. Data points are marked by the category of PM C₁ + C₂ content in quartiles. Abbreviations: C₁, Component 1; C₂, component 2; PAH, Polycyclic aromatic hydrocarbon; TNFα, tumor necrosis factor alpha.