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Features of house-dust-mite induced asthma in marmoset monkeys

: Curths, C.; Dahlmann, F.; Wichmann, J.; Becker, T.; Knauf, Y.; Kaup, F.-J.; Braun, A.; Knauf, S.

Allergy. European journal of allergy and clinical immunology 70 (2015), Supplement S101, pp.44-45
ISSN: 0105-4538
ISSN: 1398-9995
European Academy of Allergy and Clinical Immunology (Congress) <2015, Barcelona>
Fraunhofer ITEM ()

Translational animal models for human asthma are of urgent need for the preclinical testing of human specific anti-inflammatories. The common marmoset (Callithrix jacchus), a small nonhuman primate, provides a high homology to humans with the advantage of cost-saving features such as reduced body weight and a high reproduction rate. The hypothesis was that it is possible to induce an asthmatic phenotype in marmosets with allergen-specific secretion of interleukin 13 (IL13) and increased levels of lung eosinophils. Marmosets were either house dust mite allergen (HDM)- (n = 18) or sham-sensitized (n = 9). Sensitization was followed by a HDM challenge phase and therapeutic intervention with either sham- or budesonide treatment. Peripheral blood mononuclear cells (PBMC) were isolated from blood samples before and after sensitization. PBMC were seeded and stimulated with 10 lg/ml HDM w/o 50 lg/ml dexamethasone. Ninety-six hour after cultivation, supernatants were collected and evaluated for IL13 levels using a commercial ELISA Kit (UCyTech). Bronchoalveolar lavage (BAL) was performed regularly, and BAL fluid (BALF) was analyzed for cytokines and cellular composition. Post sensitization, allergen stimulated PBMCs showed higher IL13 levels compared to the baseline level (34.2 10.5, 2.5 0.7 pg/ml; mean SEM; P = 0.001 Wilcoxon test and P = 0.024 Mann-Whitney test; n = 12/6). HDM-induced IL13-release was significantly reduced by dexamethasone (1.3 0.2 pg/ml; mean SEM; P = 0.016 Wilcoxon test; n = 7). Similar results were obtained for IL13 levels of BALF supernatants. Total cell counts in BALF increased after the final HDM-challenge in all animals. Following the initial HDM challenge phase, eosinophil cell counts in BALF significantly increased for sensitized animals compared to sham-sensitized animals (Mann-Whitney test; P = 0.0030; n = 12/6). After in vivo treatment, total cell counts were significantly increased in sham-treated animals (paired t test; P = 0.0118 n = 5), in contrast to budesonide-treated animals (paired t test; P = 0.1324, n = 6). Eosinophil cells in BALF were slightly more increased in sham-treated compared to budesonide-treated animals. In conclusion, IL13 secretion of marmoset PBMCs indicates a successful sensitization against HDM. Allergen challenge of sensitized animals resulted in an increased number of lung eosinophils, one of the hallmarks of human asthma. Other readout parameters such as detection of asthma-relevant cytokine and immunoglobulin levels are under investigation.