• L Hesse, U Brouwer, A H Petersen, R Gras, L Bosman, J Brimnes, Oude ElberinkJ N GJNGGroningen Research Institute of Asthma and COPD (GRIAC), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.Division of Allergy, Department of internal medicine, University Medical Centre Groninge, van OosterhoutA J MAJMDepartment of Pathology & Medical Biology, Experimental Pulmonary and Inflammatory Research (EXPIRE), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.GSK Medicines Research Centre, Stevenage, , and M C Nawijn.
• Department of Pathology & Medical Biology, Experimental Pulmonary and Inflammatory Research (EXPIRE), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
• Clin. Exp. Allergy. 2018 Aug 1; 48 (8): 1035-1049.

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.© 2018 The Authors. Clinical & Experimental Allergy Published by John Wiley & Sons Ltd.

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