Soy biodiesel emissions have reduced inflammatory effects compared to diesel emissions in healthy and allergic mice.

Toxicity of exhaust from combustion of petroleum diesel (B0), soy-based biodiesel (B100), or a 20% biodiesel/80% petrodiesel mix (B20) was compared in healthy and house dust mite (HDM)-allergic mice. Fuel emissions were diluted to target fine particulate matter (PM(2.5)) concentrations of 50, 150, or 500 µg/m(3). Studies in healthy mice showed greater levels of neutrophils and MIP-2 in bronchoalveolar lavage (BAL) fluid 2 h after a single 4-h exposure to B0 compared with mice exposed to B20 or B100. No consistent differences in BAL cells and biochemistry, or hematological parameters, were observed after 5 d or 4 weeks of exposure to any of the emissions. Air-exposed HDM-allergic mice had significantly increased responsiveness to methacholine aerosol challenge compared with non-allergic mice. Exposure to any of the emissions for 4 weeks did not further increase responsiveness in either non-allergic or HDM-allergic mice, and few parameters of allergic inflammation in BAL fluid were altered. Lung and nasal pathology were not significantly different among B0-, B20-, or B100-exposed groups. In HDM-allergic mice, exposure to B0, but not B20 or B100, significantly increased resting peribronchiolar lymph node cell proliferation and production of T(H)2 cytokines (IL-4, IL-5, and IL-13) and IL-17 in comparison with air-exposed allergic mice. These results suggest that diesel exhaust at a relatively high concentration (500 µg/m(3)) can induce inflammation acutely in healthy mice and exacerbate some components of allergic responses, while comparable concentrations of B20 or B100 soy biodiesel fuels did not elicit responses different from those caused by air exposure alone.

Kinetic profile of influenza virus infection in three rat strains.

Influenza is a respiratory tract disease of viral origin that can cause major epidemics in humans. The influenza virus infects and damages epithelial cells of the respiratory tract and causes pneumonia. Lung lesions of mice infected with influenza virus resembles those seen in humans with influenza, and can result in severe and even fatal pneumonia. In contrast, experimental infection of rats with the virus induces a milder form of the disease, with no mortality. The purpose of the study reported here was to determine the time course of influenza infection and lung injury in Brown Norway (BN), Fischer-344 (F344), and Sprague-Dawley (SD) rats to ascertain whether genetic background impacts susceptibility to infection and host responses. Rats of each strain were inoculated intranasally with 10,000 plaque-forming units of rat-adapted influenza virus (RAIV), and lungs were assessed at postinoculation hour (PIH) 2, 24, 48, 72, and 144 for viral titer, inflammatory cells, pro-inflammatory cytokines, and biochemical indicators of lung edema (protein) and injury (lactate dehydrogenase [LD] activity). Virus titer peaked at PIH 24, and was 100-fold higher in the F344 and SD, compared with the BN strain. Alveolar macrophages, LD activity, and total protein concentration were higher in the BN rats, whereas neutrophil numbers and interleukin 6 and tumor necrosis factor-alpha activities were greatest in the bronchoalveolar lavage fluid of F344 and SD rats. The results indicate that F344 and SD rats respond in similar manner to viral infection, whereas viral replication was more limited in BN rats and was associated with a different profile of pulmonary cells.

Mortality in dioxin-exposed mice infected with influenza: mitochondrial toxicity (reye's-like syndrome) versus enhanced inflammation as the mode of action.

Increased mortality following influenza A infection was reported in B6C3F1 mice exposed to a low (0.01 micro g/kg) dose of dioxin. However, mortality was not associated with increased viral load and antibody titers to the virus were not decreased at doses of TCDD < or = 10 micro g/kg, suggesting that viral overgrowth, secondary to immunosuppression, was not the proximate cause of death. We tested the hypothesis that mitochondrial toxicity and dysfunction, similar to Reye's syndrome (RS) in humans, is responsible for increased mortality in dioxin-exposed, infected B6C3F1 female mice, based on similarities in the biochemical and immunological events that occur in RS and in TCDD-exposed animals. Endpoints were also included to test the hypothesis that increased pulmonary inflammation following dioxin exposure, in the absence of mitochondrial toxicity, was associated with increased mortality. Dose-related effects of TCDD alone, infection with influenza A alone, and combined TCDD exposure/influenza infection were evaluated. Mice were given a single ip injection of 0, 0.001, 0.01, 0.1, or 1.0 micro g TCDD/kg, 7 days before infection by intranasal instillation of an estimated LD(10-20) of influenza A Hong Kong/8/68 (H3N2) and were terminated 1, 7, and 10 days after infection. Serum, bronchoalveolar lavage fluid (BALF), and lung tissue were collected for various measurements, including clinical chemistries, cell counts, cytokine analysis, and viral titers. Exposure to < or = 1.0 micro g TCDD/kg did not increase mortality; virus titers were similar at all doses of TCDD and there was no dioxin-related effect on serum NH(3) or glucose concentrations, two prominent indicators of the altered mitochondrial oxidative metabolism typically observed in RS. A study was therefore conducted over a wider range of TCDD doses. A single injection of 0, 0.025, 0.5, or 10 micro g TCDD/kg preceded infection by 7 days; subgroups of noninfected control and highest dose group (10 micro g TCDD/kg) mice were also evaluated for biochemical and immunological endpoints on the equivalent of infection day 4 to provide baseline data. Five days after infection the same endpoints described above were evaluated. The 10 micro g TCDD/kg dose increased mortality, but once again did not increase virus titer; as in previous experiments, serum biochemistry endpoints did not support mitochondrial dysfunction. These results suggest that RS is an unlikely explanation for increased influenza mortality in TCDD-exposed mice. Rather, constituents in BALF implicate increased pulmonary inflammation as the mode of TCDD action.

Proinflammatory and Th1 cytokine alterations following ultraviolet radiation enhancement of disease due to influenza infection in mice.

Exposure of rodents to immunosuppressive agents such as ozone, dioxin, or ultraviolet radiation (UVR) leads to increased morbidity and mortality following influenza virus infection. However, these adverse effects are not related to the suppression of virus-specific immune responses. Our laboratory showed that UVR increased the morbidity, mortality, and pathogenesis of influenza virus without affecting protective immunity to the virus, as measured by resistance to reinfection, suggesting that UVR and other immunosuppressive pollutants such as dioxin and ozone may exacerbate early responses that contribute to the pathogenesis of a primary viral infection. In the present study, we examined the mechanism of UVR-enhanced mortality in the absence of effects on virus-specific immunity and tested the hypothesis that modulation of cytokine levels was associated with increased deaths and body weight loss. BALB/c mice were exposed to 8.2 kJ/m(2) UVR and were infected 3 days later with a sublethal influenza virus infection (LD(40) of mouse-adapted Hong Kong influenza A/68, H(3)N(2)). Influx of inflammatory cells, proinflammatory cytokines, and cytokines produced by T-helper lymphocytes (Th1 and Th2) were measured in lung homogenates (LH) as well as in bronchoalveolar lavage fluid (BAL). UVR preexposure decreased the influenza-induced lymphocytic influx 5 days after infection, but did not alter macrophage and neutrophil influx into the lung, or increase virus titers significantly. Although interferon (IFN)-gamma, total interleukin (IL)-12, IL-6, and TNF-alpha were altered in mice that received UVR exposure prior to infection, no clear association was made that correlated with the UVR-induced increase in body weight loss and mortality due to influenza infection.