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Subcutaneous immunotherapy suppresses Th2 inflammation and induces neutralizing antibodies, but sublingual immunotherapy suppresses airway hyperresponsiveness in grass pollen mouse models for allergic asthma

Hesse, L., Brouwer, U., Petersen, A. H., Gras, R., Bosman, L., Brimnes, J., Elberink, J. N. G. O., van Oosterhout, A. J. M. & Nawijn, M. C. Aug-2018 In : Clinical and Experimental Allergy. 48, 8, p. 1035-1049 15 p.

Research output: Contribution to journalArticle

BackgroundBoth subcutaneous and sublingual allergen immunotherapy (SCIT and SLIT) have been shown to effectively suppress allergic manifestations upon allergen exposure, providing long-term relief from symptoms in allergic disorders including allergic asthma. Clinical studies directly comparing SCIT and SLIT report a different kinetics and magnitude of immunological changes induced during treatment. Comparative studies into the mechanisms underlying immune suppression in SCIT and SLIT are lacking.

ObjectiveWe aimed to establish an experimental model for grass pollen (GP) SCIT and SLIT that would allow a head-to-head comparison of the two treatments.

MethodsBALB/c mice were sensitized with GP extract, followed by SCIT and SLIT treatments with various GP dosages. Subsequently, we challenged mice with GP and measured airway responsiveness (AHR), GP-specific immunoglobulins, ear swelling tests (EST), eosinophilic inflammation in bronchoalveolar lavage fluid (BALF), and T cell cytokine release after restimulation of lung cells (IL-5, IL-10, and IL-13).

ResultsWe find that SLIT treatment was able to suppress allergen-induced AHR, while allergic inflammation was not effectively suppressed even at the highest GP dose in this model. In contrast, SCIT treatment induced higher levels of GP-specific IgG1, while SLIT was superior in inducing a GP-specific IgG2a response, which was associated with increased Th1 activity in lung tissue after SLIT, but not SCIT treatment. Interestingly, SCIT was able to suppress Th2-type cytokine production in lung cell suspensions, while SLIT failed to do so.

Conclusions and clinical relevanceIn conclusion, GP-SCIT suppresses Th2 inflammation and induced neutralizing antibodies, while GP-SLIT suppresses the clinically relevant lung function parameters in an asthma mouse model, indicating that the two application routes depend on partially divergent mechanisms of tolerance induction. Interestingly, these data mirror observations in clinical studies, underscoring the translational value of these mouse models.

Original languageEnglish
Pages (from-to)1035-1049
Number of pages15
JournalClinical and Experimental Allergy
Volume48
Issue number8
Early online date12-May-2018
StatePublished - Aug-2018

    Keywords

  • allergic asthma, grass pollen, mouse models, subcutaneous immunotherapy, sublingual immunotherapy, tolerance induction, HOUSE-DUST MITE, REGULATORY T-CELLS, TOLERANCE INDUCTION, MURINE MODEL, RHINITIS, MICE, ANAPHYLAXIS, EFFICACY, IL-10, RESPONSES

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