R848, a Toll-like receptors 7 and 8 agonist, a potential therapy for allergic rhinitis patients.

Ghada Boghdadi, Noha Hammad, Ahmed Amer, Somaya Sammour, Samir Sorour
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引用次数: 12

Abstract

Background/purpose(s): There is a growing interest in the targeting of Toll-like receptors (TLRs) for the treatment of allergic diseases. TLRs7/8 ligands are future candidates of therapeutic value in allergic rhinitis (AR). This study focus on TLRs7/8 ligand; resiquimod (R848) as an adjuvant to immunotherapy (IT) in AR patient.

Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from atopic donors and non atopic donors. PBMCs were cultured in the absence and presence of date palm pollen allergen (Phoenix dactylifera; Pho d) and/or R848. Interleukin-4 (IL-4), IL-10, IL-13 and interferon gamma (IFN-γ) were measured in the culture supernatants.

Results: R848 was able to significantly increase the anti-inflammatory response in atopic donors more than non atopic donors. Nevertheless, the combination of both; R848 and Pho d provides inferior stimulus as compared to R848 alone in both atopic and non atopic donors.

Conclusion: Invitro treatment of PBMCs with R484 hijacks the pro inflammatory immune process triggered by TLRs7/8 to mediate anti-inflammatory response. This may provide a conception about the activity and efficacy of TLRs7/8 ligands in AR and open the gate for them to be applied in clinically in humans.

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R848, toll样受体7和8激动剂,变应性鼻炎患者的潜在治疗方法。
背景/目的:人们对靶向toll样受体(TLRs)治疗过敏性疾病越来越感兴趣。TLRs7/8配体是未来变应性鼻炎(AR)治疗价值的候选体。本研究重点关注TLRs7/8配体;雷昔莫特(R848)作为AR患者免疫治疗(IT)的辅助药物。方法:取异位和非异位供者外周血单个核细胞(PBMCs)。在不含和存在椰枣花粉过敏原(Phoenix dactylifera;博士)和/或R848。培养上清液中检测白细胞介素-4 (IL-4)、IL-10、IL-13和干扰素γ (IFN-γ)。结果:R848能显著提高特应性供者的抗炎反应,其作用优于非特应性供者。然而,两者的结合;在特应性和非特应性供体中,与单独使用R848相比,R848和phd提供的刺激较差。结论:用R484体外治疗PBMCs可劫持TLRs7/8触发的促炎免疫过程,介导抗炎反应。这可能为TLRs7/8配体在AR中的活性和功效提供一个概念,并为其在人类临床应用打开大门。
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