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 (wa shed dust and methanol extracts) on the release of proinflammatory cyt okines, interleukln-1 (IL-1), and tumor necrosis factor-alpha (TNF-alp ha) by alveolar macrophages (AM) were investigated. Rat AM were incuba ted with 0, 5, IO, 20, 50, or 100 mu g/10(6) AM/mL of DEP, methanol-wa shed DEP, or equivalent concentrations of DEP methanol extracts at 37 degrees C for 24 h. AM-conditioned supernatants were collected and ass ayed 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 a ctivity secreted by AM, whereas methanol-washed DEP had no effect. Nei ther DEP, methanol-washed DEP, nor DEP methanol extracts was found to stimulate the secretion of TNF-alpha. The effects of DEP on the releas e of IL-1 and TNF-alpha by lipopolysaccharide (LPS)- or interferon-gam ma (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-stimula ted production of IL-1 and TNF-alpha. These inhibitory effects were at tributed to the organic extracts of DEP. In contrast, stimulation of A M production of TNF-alpha by IFN-gamma was not affected by DEP exposur e. 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 expo sure.