Ovalbumin mouse models

Using a similar approach in a mouse model, Laouini et al. [67] observed that epicutaneous administration of SEB induced a systemic SEB-specific IgE antibody response and allergic skin inflammation. Savinko et al. [68] found that in ovalbumin-sensitized mice, local administration of SEB induced both SEB-specific IgE synthesis and elevated production of ovalbumin-specific IgE. Both studies concurred in finding allergic skin inflammation evinced by the presence of increased numbers of V(38+ Th2 cells and eosinophils, and expression of Th2-type cytokines and chemokines. 

We took advantage of a mouse model of allergic asthma to study the effects of nasal or bronchial applications of SEB on the development of allergic asthma in previously sensitized mice [53], Male BALB/c mice were kept under conventional pathogen-free conditions and were actively sensitized by 7 intraperitoneal injections of 10 xg ovalbumin (OVA) on alternate days from days 1 till 13 as described earlier [54], Mice were then exposed daily for 5 min to nebulized OVA (OVA mice) or saline (SAL mice) from days 33 till 37. This protocol resulted in OVA-challenged mice in the induction of bronchial eosinophilia, Th2 cytokine production, bronchial hyperresponsiveness and elevated OVA-specific IgE titers in serum as previously published [55], whereas SAL mice did not show any bronchial inflammation. One hour prior to the latter airway challenge on days 33, 35 and 37, the nose and bronchi were exposed to 10 xl of saline with or without SEB at 500 ng. 

The idea that ES-62 activity was only directed i inst Th-1 type-inflammatory diseases was questioned when it was found to be active in a mouse model of allergy—ovalbumin-induced airway hypersensitivity. As mentioned earlier, allergy is of course dependent on a Th-2 type of immune response and indeed since these data were obtained we have also witnessed a friilure of ES-62 to modulate the activity of some Thl-inducing molecules. In the airway hypersensitivity model. 

TLR9 agonists have been shown to prevent and reverse allergen-induced Th2 immune responses that are commonly observed in asthma and allergic conditions in a number of preclinical models [108], and clinical studies are underway [109]. In ovalbumin (OVA)-sensitized mouse models of asthma, agonists of TLR9... 

MDC (CCL22) and TARC (CCL17) (see Table 4.1). The role of the mouse ligand analogs has been studied in murine models of asthma. In ovalbumin-sensitized and -challenged mice. 

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