Effect of polycyclic aromatic hydrocarbons and carbon black particles on pro-inflammatory cytokine secretion: impact of PAH coating onto particles.

It has been suggested that the organic fraction of particulate matter in air pollution has a major role in the toxicity of this pollutant, notably via its effects on inflammation. The major organic compounds adsorbed onto these particles are polycyclic aromatic hydrocarbons (PAH), among which benzo[a]pyrene (B[a]P), benzo[b]fluoranthene (B[b]F), and pyrene (Pyr) are quantitatively the most important. Generally, cells or organisms are exposed to organic extracts of the particles rather than the native particles in order to study the effects of these PAH. In this study, B[a]P, B[b]F, and Pyr were tested alone and/or adsorbed onto carbon black (CB) particles differing in size in order to evaluate their impact on cytokine production (with or without LPS stimulation) by THP-1 macrophage-like cells. PAH induced significant secretion of IL-1beta, IL-8, and IL-12 after 24 or 48 hr of treatment, an effect reinforced by LPS stimulation; no effect on IL-10 secretion was noted. Fine CB particles (260 nm diameter) induced secretion of each cytokine. In general, coating the CB with PAH did not modify the effect of the CB alone; the exception was that LPS-induced IL-1beta secretion was reduced. In contrast, ultrafine CB (14 nm diameter: ufCB) caused a decrease in cytokine secretion; this effect was modified by PAH coating. For example, PAH coating on ufCB amplified the inhibitory effect of ufCB against IL-1beta secretion but did not modify IL-8 formation. Moreover, PAH coating on ufCB tended to minimize the effect of LPS stimulation; this included (i) inhibition of the decrease in IL-12 secretion induced by uncoated ufCB and (ii) stimulation of IL-10 production. It was concluded that adsorption of PAH onto these particles could decrease their bioavailability and so their abilities to affect cell cytokine production. The results also showed that when PAH were adsorbed onto the fine particles, any observed increases in cytokine secretion consistently appeared to be due to the particles themselves. In contrast, while ufCB alone almost uniformly led to decreases in cytokine formation by the cells, the added presence of the test PAHs led to variable effects - depending on whether stimulation with LPS took place or not. Thus, while some PAHs likely to be associated with PM are clearly immunomodulants, their ultimate effects in situ will likely depend on the properties of the particles themselves, in particular, their size.