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Effects of the Toll-like Receptor 4 (TLR4) Agonist Glucopyranosyl Lipid a (GLA) on Allergen-Induced Inflammation and Anaphylaxis in a Mouse Model of Peanut Allergy
Monday, March 7, 2016
South Exhibit Hall H (Convention Center)
Keith Graver, George Qian, Xiaying Wu, Li Li, Dongling Chen, Mayra Fernandez, Timothy J Soos, Christopher Arendt, El-Bdaoui Haddad
Rationale:  Glucopyranosyl Lipid A (GLA) is a synthetic TLR4 agonist with the potential to dampen or re-direct pathogenic Th2-like immune responses against specific allergens.  This study investigated the effects of GLA dosed alone or in combination with antigen in a mouse peanut allergy model.  This model is characterized by anaphylaxis, a decrease in core body temperature, an increase in peanut-specific IgE and IgG1, and an increase in Th2 cytokines.

Methods:  Female C3H/HeOuJ mice were sensitized orally with roasted peanut extract (RPE) in combination with cholera toxin.  GLA in a stable emulsion alone or in combination with RPE was introduced by the subcutaneous route on days 29, 35, 42, and 49.  Mice were challenged on day 55 by the intraperitoneal route with RPE.  The allergic response to roasted peanut extract was assessed by anaphylaxis scoring, measurement of core body temperature, serum antibody determination, and peritoneal lavage cytokine analysis.

Results:  Treatment with GLA alone or with RPE significantly reduced anaphylaxis scores and changes in core body temperature when compared to control mice.  Serum IgG1 and IgG2a levels increased with GLA/RPE treatment.  Significant increases in peritoneal lavage IL-5, IL-2, and IL-10 levels were noted with GLA/RPE treatment while no changes in serum IgE or peritoneal lavage IL-13, IL-12, and INFg were observed.

Conclusions:  These data suggest that GLA was efficacious in this rodent peanut allergy model and may have utility in a range of allergic diseases.