Suppressive effects of diesel exhaust particles on cytokine release from human and murine alveolar macrophages

Abstract

Epidemiological studies have shown an increase in the number of hospital admissions for respiratory diseases in association with high concentrations of particulate matter smaller than 10 micro m (PM(10)). Diesel exhaust particles (DEP) are important components of PM(10). This study was designed to test the effect of DEP on the release of cytokines from alveolar macrophages (AMs). Human and murine AMs were exposed to DEP for 24 hours, and the concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8 were measured in the supernatants by enzyme-linked immunosorbent assay (ELISA). DEP (10 micro g/mL) suppressed the spontaneous release of TNF-alpha and IL-6 from murine AMs (P<.05). This suppression was not seen with exposure to carbon particles. Soluble components of DEP had a similar suppressive effect, suggesting that the chemical composition of DEP is responsible for the suppression. Lipopolysaccharide (LPS)- or IFN-gamma-induced TNF-alpha and IL-6 production by murine AMs were suppressed by DEP in a dose-dependent manner (P<.05). DEP also inhibited LPS-stimulated production of TNF-alpha, IL-6, and IL-8 from human AMs (P<.05). Pretreatment of AMs with superoxide dismutase (SOD) (300 IU/mL) prevented the suppressive effect of DEP on AM cytokine production (P<.05). The authors conclude that DEP exposure suppressed the release of cytokines from AMs, and speculate that this suppression could impair normal host defenses.