Effects of diesel exhaust particles on the release of interleukin-1 and tumor necrosis factor-alpha from rat alveolar macrophages

The effects of diesel exhaust particles (DEP) and their components (washed dust and methanol extracts) on the release of proinflammatory cytokines, interleukln-1 (IL-1), and tumor necrosis factor-alpha (TNF-alpha) by alveolar macrophages (AM) were investigated. Rat AM were incubated with 0, 5, IO, 20, 50, or 100 mu g/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 lL-1 and TNF-alpha. At high concentrations, both DEP and DEP methanol extracts were shown to increase IL-l-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-1 and TNF-alpha by lipopolysaccharide (LPS)- or interferon-gamma (IFN-gamma)-primed AM were also studied. AIM were preincubated with various concentrations of DEP for 2 h, then challenged with either 0.1 mu g/mL of LPS or 5 units/mL of IFN-gamma. DEP inhibited LPS-stimulated production of IL-1 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 AIM to LPS stimulation may be a contributing factor to the impairment of pulmonary defense system after prolonged DEP exposure.