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The authors investigated the effects of inhalation of diesel exhaust (DE) on murine mycobacterial infection in vivo. Eight-week-old female BALB/c mice were exposed to DE (3 mg/m 3 of diesel exhaust particles [DEPs]) for 1 month, 2 months, or 6 months (for 7 hours a day, 5 days a week). Control mice were housed in a clean room for the same periods. On the day following the last DE exposure, control mice and DE-exposed mice were aerially infected with Mycobacterium tuberculosis (1?×?10 6 colony-forming units (CFU), Kurono strain). At 7 weeks after mycobacterial infection, the authors examined the lung tissues for histopathological changes and performed reverse transcriptase–polymerase chain reaction (RT-PCR) to measure the messenger RNA (mRNA) expression of several proinflammatory cytokines and inducible nitric oxide synthase (iNOS). Then, the homogenates of lungs and spleens were cultured on 1% ( v / v ) Ogawa's egg slant medium, and after a 4-week incubation period at 37°C, colonies on the medium were counted. After 1 month of DE exposure, the mycobacterial infection had slightly ameliorated. After 2 months of DE exposure, the expression levels of tumor necrosis factor (TNF)-a, interleukin (IL)-1ß, IL-12p40, interferon (IFN)-?, and iNOS mRNAs were slightly increased. However, after 6 months of DE exposure, the expression levels of IL-1ß, IL-12p40, IFN-?, and iNOS mRNAs were decreased, and the infection as measured by increased lung burden (CFU) actually increased. These results indicate that long-term DE exposure may increase pulmonary mycobacterial burden. [ABSTRACT FROM AUTHOR]

The authors investigated the effects of exposure to diesel exhaust (DE) on murine lung tissues invivo. BALB/c and C57BL/6 mice were exposed to DE with low (100 μg/m 3 ) and high (3 mg/m 3 ) DE particle levels for 3 months. The authors then examined morphological changes and the expression of mRNAs for various cytokines (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, IL-4, IL-6, IL-10, IL-12p40, and interferon [IFN]-γ) and inducible nitric oxide synthase (iNOS) in the lungs, as well as TNF-α, IL-1β, IL-10, IL-12p40, and Mac-1 mRNA expression in alveolar macrophages (AMs). TNF-α, IL-12p40, IL-4, and IL-10 mRNA expression were mildly increased, whereas IL-1β mRNA and iNOS expression were slightly decreased, in the low- and high-level exposure groups. Flow cytometry of bronchoalveolar lavage fluid revealed a significant increase in Mac-1-positive cells in the high-level exposure group. On histological examination, bronchus-associated lymphoid tissue (BALT), containing B and T lymphocytes, had developed only in the high-level exposure group. Chronic inhalation of DE influences cytokine expression in the murine lung, and induces phagocytosis and BALT development. These findings suggest that DE may provoke immunological responses by acting as a foreign body in the lung, and that even low-level exposure may induce allergic reactions. [ABSTRACT FROM AUTHOR]

The authors investigated the effect of diesel exhaust (DE) on cytokine expression in murine lung tissues. BALB/c mice were exposed to DE for 1 month at different dose levels of DE (low dose: diesel exhaust particles [DEP] 100 µg/m[sup 3]; high dose: 3mg/m[sup 3]). After exposure, the authors examined mRNA expression of cytokines (tumor nocrosis factor alpha [TFN-α], Interleukin [IL]-1β, IL-4, IL-6, IL-10, IL-12p40, and interferon gamma [IFN-γ] and inducible nitric oxide synthase (iNOS) in the lung, and also measured the secretion of TNF-α and IL-10 protein by alveolar macrophages (AM). The mRNA expression levels of inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-12p40, IFN-γ) and iNOS, which are important for host defense, were suppressed significantly. However, the IL-10 mRNA level was increased by DE exposure. The IL-4 mRNA level was increased by low-dose DE exposure but suppressed by high-dose DE exposure. TNF-α and IL-10 secretion by AM paralleled mRNA expression. Chronic inhalation of DE affects cytokine expression in murine lung. These results suggest that DE alters immunological responses in the lung and may increase susceptibility to pathogens, and that increased IL-4 expression by low-dose DE exposure may induce allergic reaction such as asthma. [ABSTRACT FROM AUTHOR]

To investigatethe effects of diesel exhaust particles (DEP) and mycobacterial infection on macrophages, we examined protein and mRNA expression levels of various cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-12, and IL-18 in BALB/c mouse alveolar macrophages (AM)and a macrophagecell line (RAW264.7) after in vitro stimulation with diesel exhaust (DE), with and without Mycobacterium bovis bacillus Calmette-Guerin (BCG). The cells were exposed to DE freshly generated in an in vitro system. When AM were exposed to DE (mean DEP exposure level, 300 µ g/m[sup 3]), the levels of TNF-α and IL-12 decreased significantly (by 51% to 61% for TNF-α and by 69% to 78% for IL-12), whereas those of IL-1β and IL-18 remained unchanged. When AM were exposed to DE and then treated with BCG, the level of TNF-α decreased by 45% to 71%, whereas the level of IL-1β increased by 154%, compared with AM treated with BCG alone. Similarly, RAW264.7 cells were stimulated with DE with and without M. bovis BCG and cytokine mRNA levels examined by reverse transcriptase-polymerase chain reaction (RT-PCR). Longer exposure to DE decreased TNF-α and IL-12 mRNA levels in the RAW264.7 cells. When the cells were exposed to DE and subsequently treated with BCG, levels of TNF-α, IL-1β, and IL-12 mRNAs decreased compared with those of cells treated with BCG alone. These results show that DE exposure has complex and diverse effects on cytokine production by AM, and that longer exposure (> 8 hours) may suppress cytokine production by AM in vitro. Longer exposure of DE may therefore suppress the host defense in the lung and may increase susceptibility to lung infections such as mycobacterial infection. [ABSTRACT FROM AUTHOR]