Extent of allergic inflammation depends on intermittent versus continuous sensitization to house dust mite.

OBJECTIVE: House dust mite (HDM) exposure is used to model experimental asthma in mice. However, a direct comparison of inflammatory responses following continuous versus intermittent HDM exposure has not been reported. Therefore, we investigated whether the HDM dose at sensitization or challenge affects extent of inflammation in mice that were either continuously or intermittently sensitized with HDM. MATERIALS AND METHODS: C57BL/6 mice received either 10 continuous exposures with 10 µg HDM per exposure or two intermittent HDM exposures over a period of two weeks and were subsequently challenged by three instillations with HDM during the third week. For the intermittent model, mice were sensitized with 1 or 10 µg HDM and challenged on three consecutive days with 1 or 10 µg HDM. Inflammatory cells in the bronchoalveolar lavage fluid and epithelial cell hyperplasia and mucous cell metaplasia were quantified. RESULTS: Significantly higher levels of inflammation and mucous cell metaplasia were observed when mice were sensitized intermittently compared with continuously. Intermittent sensitization and challenge with 10 µg HDM caused maximum inflammation, mucous cell metaplasia, and epithelial cell hyperplasia. However, sensitization with 1 µg HDM only also showed increased inflammation when challenged with 10 µg HDM. DISCUSSION: These findings suggest major differences in adaptive immunity, depending on the sensitization protocol. CONCLUSIONS: Because of significant differences, the HDM sensitization protocol should be carefully considered when designing studies to investigate the underlying mechanisms of immunity in mouse models of asthma.

Modulators of cigarette smoke-induced pulmonary emphysema in A/J mice.

Mice develop pulmonary emphysema after chronic exposure to cigarette smoke (CS). In this study, the influence of gender, exposure duration, and concentration of CS on emphysema, pulmonary function, inflammation, markers of toxicity, and matrix metalloproteinase (MMP) activity was examined in A/J mice. Mice were exposed to CS at either 100 or 250 mg total particulate material/m(3) (CS-100 or CS-250, respectively) for 10, 16, or 22 weeks. Evidence of emphysema was first seen in female mice after 10 weeks of exposure to CS-250, while male mice did not develop emphysema until 16 weeks. Female mice exposed to CS-100 did not have emphysema until 16 weeks, suggesting that disease development depends on the concentration and duration of exposure. Airflow obstruction and increased pulmonary compliance were observed in mice exposed to CS-250 for 22 weeks. Decreased elasticity was likely the major contributor to airflow obstruction because substantial remodeling of the conducting airways, beyond mild mucous cell hyperplasia, was lacking. Exposure to CS increased the number of macrophages, neutrophils, lymphocytes (B cells and activated CD4- and CD8-positive T cells), and activity of MMP-2 and -9 in the bronchoalveolar lavage fluid (BALF). Treatment with antioxidants N-acetylcysteine or epigallocatechin gallate (EGCG) did not decrease emphysema severity, but EGCG slightly decreased BALF inflammatory cell numbers and lactate dehydrogenase activity. Inflammation and emphysema persisted after a 17-week recovery period following exposure to CS-250 for 22 weeks. The similarities of this model to the human disease make it promising for studying disease pathogenesis and assessing new therapeutic interventions.