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TLR4 Agonist GLA Modifies Th1/Th2 Cytokine Profiles in PBMC from Patients with Pollen Allergy
Monday, March 7, 2016
South Exhibit Hall H (Convention Center)
Hailing Lu, MD PhD, Richard Roque, Jan ter Meulen, MD, Christopher Clegg, PhD
Rationale: T helper (Th) 2 cytokines promote the development of an allergic inflammatory response in allergic individuals.  Th1 cytokines can counterbalance the Th2 immune response and aid in treatment of allergic diseases.  The goal of this study was to evaluate the potential of using Glucopyranosyl Lipid A (GLA), a synthetic TLR4 agonist, to modify Th1/2 cytokine responses to grass pollen allergen in PBMC from allergic donors.

Methods: Peripheral blood mononuclear cells (PBMC) were collected from 12 subjects with allergy to Timothy grass pollen and cultured with grass pollen Phleum pretense extract (10 ug/mL), with or without GLA (1 ug/mL) for 6 days.  Cytokine production was measured by ELISA and Luminex assays.

Results: The levels of Th2 cytokines, IL-5 and IL-13, were significantly decreased in the presence of GLA.  IL-5 was 213±72 pg/mL in the allergen alone group vs. 60±17 pg/mL in the allergen plus GLA group (p=0.02).  IL-13 was 635±140 pg/mL in the allergen alone group vs. 322±75 pg/mL in allergen plus GLA group (p=0.006).  Th1 cytokines, IFNγ and IL-12, were significantly increased in the presence of GLA.  IFNγ was 1008±378 pg/mL in the allergen alone group vs. 3842±876 pg/mL in the allergen plus GLA group (p=0.001).   IL-12p40 was 126±48 pg/mL in allergen alone group vs. 898±179 pg/mL in allergen plus GLA group (p=0.0004).  Anti-IL12 neutralizing antibody inhibited GLA-induced IFNy significantly (p=0.0002).

Conclusions: GLA can decrease grass pollen extract induced Th2 cytokines and increase Th1 cytokines.  These results support testing of GLA in pollen-allergic patients in the setting of desensitization.