Effects of Diesel Exhaust Particles on the Release of Interleukin-1 and Tumor Necrosis Factor-Alpha from Rat Alveolar Macrophages

Abstract

The effects of diesel exhaust particles (DEP) and their components (washed dust and methanol extracts) on the release of proinflammatory cytokines, interleukin-I (IL-1), and tumor necrosis factor-alpha (TNF-alpha) by alveolar macrophages (AM) were investigated. Rat AM were incubated with 0, 5, 10, 20, 50, or 100 micrograms/10(6) AM/mL of DEP, methanol-washed DEP, or equivalent concentrations of DEP methanol extracts at 37 degrees C for 24 h. AM-conditioned supernatants were collected and assayed for the activities of IL-1 and TNF-alpha. At high concentrations both DEP and DEP methanol extracts were shown to increase IL-I-like activity secreted by AM, whereas methanol-washed DEP had no effect. Neither DEP, methanol-washed DEP, nor DEP methanol extracts was found to stimulate the secretion of TNF-alpha. The effects of DEP on the release of IL-I and TNF-alpha by lipopolysaccharide (LPS)- or interferon-gamma (IFN-gamma)-primed AM were also studied. AM were preincubated with various concentrations of DEP for 2 h, then challenged with either 0.1 microgram/mL of LPS or 5 units/mL of IFN-gamma. DEP inhibited LPS-stimulated production of H-I and TNF-alpha. These inhibitory effects were attributed to the organic extracts of DEP. In contrast, stimulation of AM production of TNF-alpha by IFN-gamma was not affected by DEP exposure. In summary, evidence that DEP enhanced the production of IL-1 by AM in vitro suggests that this proinflammatory cytokine may play a role in the pulmonary response to DEP inhalation. The suppressive response of DEP-pretreated AM to LPS stimulation may be a contributing factor to the impairment of pulmonary defense system after prolonged DEP exposure.