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Repeated exposure to diesel exhaust particles causes suppression of cell-mediated immune responses to listeria infection in Brown Norway rats.

Yin-XJ; Dong-CC; Ma-JY; Antonini-JM; Roberts-JR; Ma-JK
Toxicologist 2004 Mar; 78(S-1):99-100
Diesel exhaust particles (DEP) have been shown to alter pulmonary immune responses to bacterial infection. However, the in vivo effect of DEP exposure on the T cell-mediated immune responses against bacterial infection has not been clearly demonstrated. Here, we examined the effects of repeated DEP exposure on pulmonary responses to bacterial infection. Brown Norway rats were exposed to DEP by inhalation at 20.62 +/- 1.31 mg/m 3 , 4 hr/day for 5 days, followed by intratracheal inoculation with 100, 000 Listeria at 2 hours after the last DEP exposure. DEP-exposed rats showed a significant increase in lung bacterial load at both 3 and 7 days post-infection. The repeated DEP exposure was shown to suppress both the innate, orchestrated by alveolar macrophages (AM), and T-cell mediated responses to Listeria. DEP inhibited production of interleukin-B (IL-1B ), tumor necrosis factor-a , and IL-12 by AM, but enhanced Listeria-induced production of IL-10, which has been shown to prolong the survival of intracellular pathogens such as Listeria. DEP exposure also suppressed the development of bacteria-specific lymphocytes from lung-draining lymph nodes, as indicated by the decreased numbers of T lymphocytes and their CD4 + and CD8 + subsets. In addition, the DEP exposure markedly inhibited the Listeria-induced lymphocyte secretion of IL-2 at day 7, IL-10 at days 3 and 7, and interferon-y at days 3 to 10 post-infection when compared to air-exposed controls. These results show a sustained pattern of down-regulation of T-cell mediated immune responses by repeated low-dose DEP exposure, which is different from the results of a single high dose exposure (100 mg/m3, 4 hours), where the acute effect of DEP aggravated bacteria infection but triggered a strong T cell-mediated immunity.
Diesel-exhausts; Exposure-levels; Immune-reaction; Laboratory-animals; Animals; Animal-studies; Bacterial-infections; Pulmonary-system-disorders; Lung-disorders; Particulates; Aerosols
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The Toxicologist. Society of Toxicology 43nd Annual Meeting and ToxExpo, March 21-25, 2004, Baltimore, Maryland