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.

Inconsistencies between cytokine profiles, antibody responses, and respiratory hyperresponsiveness following dermal exposure to isocyanates.

Cytokine profiling of local lymph node responses has been proposed as a simple test to identify chemicals, such as low molecular weight diisocyanates, that pose a significant risk of occupational asthma. Previously, we reported cytokine messenger RNA (mRNA) profiles for dinitrochlorobenzene (DNCB) and six isocyanates: toluene diisocyanate, diphenylmethane-4,4'-diisocyanate, dicyclohexylmethane-4,4'-diisocyanate, isophorone diisocyanate, p-tolyl(mono)isocyanate, and meta-tetramethylene xylene diisocyanate. The present study was conducted to test the hypothesis that relative differences in the cytokine profile are predictive of relative differences in total serum immunoglobulin (Ig) E and respiratory responses to methacholine (Mch) following dermal exposure to the chemicals. After a preliminary experiment to determine an exposure regimen sufficient to achieve responses to Mch following dermal diisocyanate exposure, BALB/c mice received nine dermal exposures over a period of 28 days to one of six isocyanates, DNCB, or vehicle. Mice were then challenged with increasing doses of Mch and responsiveness was assessed using whole-body plethysmography. Serum antibody responses and cytokine mRNA profiles in the draining lymph node were also assessed. In separate experiments, cytokine protein assays were performed after five dermal exposures over a 14-day period. The response pattern for interleukin (IL)-4, IL-10, and IL-13 for the different isocyanates was highly reproducible as determined by RNAse protection assay, reverse transcription-PCR, or cytokine protein levels. However, the relative differences in T-helper cytokine profiles were not predictive of relative differences in either total serum IgE or respiratory responses to Mch following dermal exposure. The data suggest that the cytokine profiling approach needs to be further developed and refined before adoption and that other approaches to hazard identification should be pursued as well. Based on the weight of evidence from all the assays performed, it appears that all six isocyanates tested have some potential to cause respiratory hypersensitivity following dermal exposure.

Ultraviolet radiation downregulates allergy in BALB/c mice.

The immunosuppressive effects of exposure to ultraviolet radiation (UVR) are well known and the underlying mechanisms extensively studied. The suppression of Th1 appears to account for UVR suppression of contact hypersensitivity and delayed-type hypersensitivity responses and increased susceptibility to certain infections and tumor development. The underlying mechanisms suggest Th2-mediated responses associated with immediate-type hypersensitivity and allergic lung disease should be unchanged or possibly enhanced by UVR. The hypothesis that UVR exposure enhances allergic lung disease in BALB/c mice was tested. Effects of UVR on sensitization and elicitation of respiratory hypersensitivity were assessed using a fungal extract, Metarhizium anisopliae (MACA), as the allergen. BALB/c mice were sham or UVR (8 KJ/m(2)) exposed 3d before involuntary aspiration (IA) of MACA or vehicle. The mice received UVR exposures before the first and second of three IAs in the sensitization protocol and 3 d before the fourth IA in the elicitation protocol. Serum and bronchoalveolar lavage fluid (BALF) were harvested before (d 21, sensitization/d 24, elicitation) and at 1 (d 22/d 28), 3 (d 24/d 29), and 7 (d 28/d 35) d following the last IA. UVR exposure prior to sensitization suppressed two hallmarks of allergic disease, immune-mediated inflammation (eosinophil influx) and total immunoglobulin (Ig)E compared to the sham-UVR controls. There were no differences attributable to UVR exposure in previously sensitized mice. These data suggest that UVR exposure prior to sensitization suppresses allergic responses but has no effect on the elicitation of allergic responses in previously sensitized individuals. Consequently, there is no evidence that exposure to UVR enhances the induction or expression of allergic lung disease.

A murine model for low molecular weight chemicals: differentiation of respiratory sensitizers (TMA) from contact sensitizers (DNFB).

Exposure to low molecular weight (LMW) chemicals contributes to both dermal and respiratory sensitization and is an important occupational health problem. Our goal was to establish an in vivo murine model for hazard identification of LMW chemicals that have the potential to induce respiratory hypersensitivity (RH). We used a dermal sensitization protocol followed by a respiratory challenge with the evaluation of endpoints typically associated with RH in human disease. Trimellitic anhydride (TMA) was used as a prototype respiratory sensitizer and was compared to the dermal sensitizer; 2,4-dinitrofluorobenzene (DNFB), along with vehicle controls. BALB/c mice were dermally sensitized using two exposure protocols. Mice in both protocols were dermally exposed on experimental days; D-18 and D-17 (abdomen), and D-13 (ear). On D 0 mice received an intratracheal (IT) challenge. The mice in Protocol 2 were abdominally exposed twice with the addition of exposures on D-25 and D-24. Results indicate that mice required the additional dermal sensitization and the IT challenge (Protocol 2) to significantly elevate total IgE in serum and bronchoalveolar lavage fluid (BALF). Additional responses suggestive of RH were seen following Protocol 2, including increases in BALF cell numbers and neutrophils post IT with TMA (but not DNFB). These data suggest that the dermal sensitization and IT challenge followed by evaluation of serum antibodies and lung parameters are a reasonable and logistically feasible approach towards the development of a model for RH responses to LMW chemicals.