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A translational non-human primate model for human asthma in the common marmoset (Callithrix Jacchus)

: Curths, Christoph; Wichmann, Judy; Becker, Tamara; Kaup, Franz-Josef; Hohlfeld, Jens M.; Sewald, Katherina; Windt, Horst; Dunker, Sarah; Braun, Armin; Knauf, Sascha

American Journal of Respiratory and Critical Care Medicine 187 (2013), Supplement, Art. A2687
ISSN: 1073-449X
ISSN: 0003-0805
ISSN: 1535-4970
American Thoracic Society (ATS International Conference) <2013, Philadelphia/Pa.>
Journal Article, Conference Paper
Fraunhofer ITEM ()

Currently, the most commonly used species in animal models for human asthma are rodents. Unfortunately, they are often limited in reflecting the human anatomical, physiological, and immunological situation and new models are essentially needed to test human specific anti-inflammatory drugs.
Common marmoset monkeys (Callitrix jacchus), a new world non-human primate, were sensitized against house dust mite (HDM) allergen (n=5). Dermatophagoides pteronyssinus extract (10 mcg, Greer) in combination with 1.5 mg aluminum hydroxide (Thermo Scientific) was subcutaneously injected once a week over a period of six weeks. A skin-prick test was carried out pre and post sensitization. Animals were challenged with HDM allergen aerosol, 2-4 months after sensitization on two consecutive days per week, over a period of three weeks.
Under general anesthesia, each animal received the increasing dosage of 2x0.5 (wk 1), 2x1.0 (wk 2), 1x2.5 and 5 ?g HDM (wk 3) intratracheally via microsprayer. The inflammatory status of the lung was monitored by bronchoalveolar lavage (BAL) pre and post aerosol challenge. Invasive lung function measurements were conducted to evaluate allergen induced airway hyperreactivity (AHR) towards methacholine (MCh) provocation. Naïve (n=11) and non-sensitized but HDM-challenged animals (n=2) served as controls.
The success of sensitization in HDM-treated animals was indicated by positive skin-prick test reactions towards D. pteronyssinus antigen.
Furthermore, aerosol HDM provocation induced a remarkable eosinophil increase in the lungs of sensitized animals. Eosinophil levels in BAL elevated from 0±0 % baseline level to 53±12 % post provocation level. Lymphocyte amounts pre- (8±2 %) and post-provocation (5±1%) showed only minor differences (mean±SEM, n=4). IL-13 cytokine levels in BAL fluid of sensitized marmosets were before and after HDM challenge 0.5 and 21.2 pg/ml (median, n=4), respectively.
Sensitized animals showed an airway hyperreactivity in response to methacholine during invasive lung function measurements. The provocative dose (PD) of MCh that induced a 150% increase of lung resistance from baseline was significantly decreased in sensitized (PD 150=0.60 mcg, n=5) compared to naïve marmosets (PD150=1.18 mcg, median, n=11, p=0.037).
Sensitization of the non-human primate common marmoset with HDM induced an asthmatic phenotype with the characteristic hallmarks of asthma like lung eosinophilia and airway hyperreactivity. These results provide the basis for the establishment of a translational animal model for preclinical testing of new human specific anti-inflammatory drugs for the treatment of asthma.