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Background Asthma is a multifaceted disease that presents with a combination of reversible bronchoconstriction, inflammation, and airway remodeling. Historically, a variety of in vivo models have been used by preclinical investigators as surrogates for the disease. However, many of these models have significant limitations. For example, rodent models relying solely on TH2 mediated respiratory inflammation have inadequate predictability and clinical translatability because they can only recapitulate partial aspects of the human disease. In order to align with human Phase I allergen challenge experiments we used ascaris sensitive sheep model. This model enables us to investigate role of different mechanisms on early and late asthmatics responses.

Background The ovalbumin (OVA) sensitized and challenged Brown Norway (BN) rat model is a practical PD model often used to determine the impact of drug treatment on late phase lung inflammation. However, the sole measurement of bronchoalveolar lavage fluid (BALF) inflammatory cells does not always correlate into human efficacy for respiratory diseases such as asthma. Added value to this rodent model may be derived by a deeper understanding of the relationship between disease-related cytokine secretion and inflammation.

Background Spleen Tyrosine Kinase (SYK) is a key activator of signaling pathways downstream of multiple surface receptors implicated in asthma. SYK function has been extensively studied in Last cells downstream of the high-affinity IgE receptor (FceR1). Most studies evaluating SYK function in preclinical models have relied on poorly selective compounds, anti-sense oligonucleotides, or SYK knockout mice. Here we describe the characterization of SYK mechanism in multiple in vivo model settings.