Alteration of pulmonary immunity to Listeria monocytogenes by diesel exhaust particles . I. Effects of DEPs on early pulmonary responses

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Cytokines in BAL fluid. The concentrations of IL-1[beta], TNF-[alpha], and IL-12 in BAL fluid obtained from various treatment groups are shown in Figure 3. At 3 days postexposure, Listeria infection resulted in a significant increase in IL-1[beta] in both air-exposed and the lower-dose DEP-exposed rats. DEP exposure at the higher dose appeared to enhance IL-1[beta] levels in the BAL fluid. In the combined high-dose DEP/Listeria exposure, however, the concentration of IL-1[beta] was significantly lower than those in animals exposed to DEP or Listeria alone. The BAL fluid of control rats contained relatively low concentrations of TNF-[alpha]. DEP exposure did not affect the production of TNF-[alpha], but the BAL levels of TNF-[alpha] from Listeria-treated rats were significantly higher than those of the noninfected rats at 3 days postexposure. Listeria infection strongly induced the production of IL-12 at 3 days postexposure. DEP exposure, which had little or no effect on the BAL level of IL-12, significantly inhibited Listeria-induced IL-12 production. At day 7, the concentrations of various cytokines in the BAL fluid from DEP- and/or Listeria-exposed rats were not different from the corresponding cytokine levels obtained from the air-exposed control.

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Cytokines in AM-conditioned media. The effects of DEP exposure on the spontaneous release of IL-1[beta], TNF-[alpha], and IL-12 by AMs from rats with or without Listeria infection was determined. The high-dose DEP exposure enhanced the spontaneous release of IL-1[beta] by AMs (Figure 4A). This increase was dose dependent, and the higher dose of DEP exposure (100 mg/[m.sup.3]) showed significant stimulatory effect at both 3 and 7 days postexposure. AMs from Listeria-infected rats also showed increased secretion of IL-1[beta] at 3 days postinfection. This increase was markedly suppressed by DEPs at both exposure doses. The spontaneous release of TNF-[alpha] by AMs was not affected by DEP exposure but was significantly enhanced by Listeria infection (Figure 4B) at 3 days postexposure. DEPs also had no effect on TNF-[alpha] secretion in Listeria-infected rats. At day 7, the spontaneous release of TNF-[alpha] by AMs from all rats decreased to near basal level. Figure 4C shows that DEP exposure alone had no effect on AM secretion of IL-12. Listeria, on the other hand, induced AM secretion of IL-12 at 3 days postexposure. In the combined exposure, however, Listeria-induced IL-12 secretion was significantly suppressed by DEPs at both 3 and 7 days postexposure.

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Figure 5 shows the secretion of IL-1[beta], IL-12, and TNF-[alpha] by AMs in response to ex vivo LPS challenge using cells obtained from various exposure groups. A comparison of Figures 4 and 5 shows that LPS has a general stimulatory effect on AM secretion of these proinflammatory cytokines. Listeria-infected AMs, however, showed an increased response to LPS in the secretion of IL-1[beta] compared with the air control (Figure 5A). DEP-exposed AMs showed little to moderate response to LPS stimulation. But in the combined exposure group, the Listeria-induced secretion of IL-1[beta] was significantly reduced by DEPs at both exposure doses and at 3 and 7 days postexposure. Figure 5B shows that the secretion of TNF-[alpha] by AMs under Listeria and/or LPS stimulation was significantly inhibited by DEPs in a dose-dependent manner at both 3 and 7 days postexposure. The effect of DEPs on macrophage secretion of IL-12 is shown in Figure 5C. Listeria-infected AMs showed increased response to LPS stimulation in the production of IL-12 compared with AMs obtained from air-exposed rats. DEP exposure, which had no effect on the secretion of IL-12 by noninfected AMs, inhibited the production of the same cytokine by AMs from rats exposed to Listeria. This DEP effect was found significant at the higher DEP exposure dose at both 3 and 7 days postexposure.