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There is increasing evidence for a role of pulmonary surfactant in asthma and allergic inflammation. In murine asthma models, recent studies have demonstrated that surfactant components downregulate the allergic inflammation. Therefore, we tested the hypothesis that in individuals with mild asthma, a natural porcine surfactant preparation (Curosurf) given before segmental allergen challenge can reduce the allergic airway inflammation. Ten patients with asthma and five healthy control subjects were treated in two segments with either Curosurf or vehicle followed by local allergen challenge. Six additional patients with asthma received Curosurf before allergen challenge in one segment as above, but the second segment was instilled with Curosurf without allergen challenge. Unexpectedly, surfactant treatment augmented the eosinophilic inflammation 24 hours after allergen challenge. A direct chemotactic effect of Curosurf was excluded. However, levels of eotaxin and interleukin-5 were increased in bronchoalveolar lavage after Curosurf treatment, whereas IFN-gamma-levels and numbers of IFN-gamma(+) T cells were decreased. Curosurf had no influence on spreading and retention of allergen determined by allergen uptake in mice. These findings demonstrate that treatment with a natural porcine surfactant results in an augmentation of the eosinophilic inflammation after allergen challenge that is more likely due to immunomodulatory effects than to biophysical properties of the surfactant.

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Background: GATA-3 (GATA binding protein 3) and the proto-oncogene c-maf are Th2-regulating transcription factors that control the expression of interleukin (IL)-4 and IL-5, while T-bet (T-box expressed in T cells) is a Th1-specific transcription factor that controls the expression of interferon (IFN-γ). Allergen provocation in asthmatics induces a Th2-dominated cytokine profile, but so far it is unknown whether the skewed cytokine expression is reflected by the expression of the respective transcriptional regulators. Objective: The aim of this study was to determine the regulation of Th1- and Th2-specific transcription factors and cytokines in 10 atopic subjects with mild asthma and 5 nonatopic healthy controls at baseline and after segmental sham and allergen challenge. Methods: The mRNA expression of GATA-3, c-maf and T-bet was determined by real-time polymerase chain reaction in bronchoalveolar lavage (BAL) cells and bronchial biopsies. The percentage of IL-4+, IL-5+ and IFN-γ+ BAL T cells was determined by flow cytometry, and BAL levels of these cytokines were measured by ELISA. Results: In BAL cells of asthmatics, the mRNA expression of all transcription factors was increased after allergen challenge. In bronchial biopsies, the basal expression of GATA-3 was increased in asthmatics compared to healthy controls but decreased after allergen challenge. Compared to sham challenge, the percentage of IL-5+/CD4+ BAL T cells was increased after allergen challenge in asthmatics while the percentage of IFN-γ+/CD4+ and IFN-γ+/CD8+ T cells was decreased. Expression of c-maf mRNA in BAL cells correlated with IL-4+/CD4+ BAL cells and BAL IL-5 levels. Conclusions: Segmental allergen challenge in asthmatics leads to increased GATA-3, c-maf and T-bet expression in BAL cells but not in bronchial biopsies.

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