Resiquimod, a new immune response modifier from the family of imidazoquinolinamines, inhibits allergen‐induced Th2 responses, airway inflammation and airway hyper‐reactivity in mice

Abstract

These data indicate that R-848 effectively inhibits allergen-induced airway inflammation and hyper-reactivity by modulation of increased Th2-immune responses.

TLR3 but Not TLR7/8 Ligand Induces Allergic Sensitization to Inhaled Allergen

“…In addition, systemic treatment of sensitized animals during primary challenge (37) or during secondary Ag challenge (36) again reduced allergic airway disease. Application of TLR ligands into the lung prior to airway challenge efficiently prevents induction of allergic diseases probably by a mechanism depending on CD8 + T cells (38). Moreover, viral TLR ligands given prior to and during allergen challenge seem to be able to modulate already established Ig responses and also the development of the developing allergic airway disease (39).…”

“…For intracellular cytokine analysis, we used allophycocyanin-labeled IFN-g (BD Pharmingen), PE-labeled IL-17A (BD Pharmingen), and PE-labeled IL-5 (BD Pharmingen). Abs were incubated at 4˚C for [30][31][32][33][34][35][36][37][38][39][40] ), single-cell suspensions of tracheal lymph nodes or lung cells were adjusted and surface stained for PeCy7-labeled CD4 PeCy7 and PE-labeled CD25 (all BD Pharmingen) as described. Foxp3 staining was performed following the advice of the manufacturer of the fixation/permeabilization set (eBioscience).…”

Treatment with the TLR7 agonist R848 induces regulatory T‐cell‐mediated suppression of established asthma symptoms

“…Mouse models of allergic asthma have long been used to dissect the immunological mechanisms leading to asthma, and despite the heterogeneity of experimental protocols in terms of strain differences, type and dose of antigen, time and route of administration, most studies have provided evidence for protective effects of natural or synthetic TLR2, TLR4, or TLR9 ligands in allergen-induced lung inflammation [1][2][3][4][5]. Similarly, the synthetic ligand of TLR7, R848 (or resiquimod), has been reported to prevent typical respiratory syndromes (airway hyperresponsiveness) and allergic inflammation (recruitment of eosinophils to the lung, production of IgE Abs, and Th2-driven cytokine production) [5][6][7][8] in treated mice. R848 was initially developed as a potential antiviral agent and exerts its immunostimulatory function via mouse TLR7 as well as human TLR7 and TLR8 [9,10].…”

“…Similarly, the synthetic ligand of TLR7, R848 (or resiquimod), has been reported to prevent typical respiratory syndromes (airway hyperresponsiveness) and allergic inflammation (recruitment of eosinophils to the lung, production of IgE Abs, and Th2-driven cytokine production) [5][6][7][8] in treated mice.…”

“…Hence, we set up an acute asthma model with well-established allergic hallmarks to assess whether TLR7 stimulation could suppress as well as prevent these symptoms. Our protocol differed from those currently used for asthma prevention, insofar as R848 was given at the end rather than at the beginning of a series of OVA challenges, once disease symptoms were manifest [7,8,12]. Other investigators have reported the suppression of established asthma after in vivo treatment with the TLR7 agonist between a first and a second series of allergen challenges at an interval of 3-4 wk [8].…”