Increased nasal mucosal interferon and CCL13 response to a TLR7/8 agonist in asthma and allergic rhinitis

BackgroundAcute respiratory viral infections are a major cause of morbidity and mortality, especially in patients with preexisting lung diseases such as asthma. Toll-like receptors critical the early detection viruses activating innate immunity mucosa, but there is no reliable convenient method by which mucosal immune responses can be measured.ObjectiveWe sought to assess vivo an stimulus compare responsiveness between healthy volunteers allergy.MethodsWe administered receptor 7/8 agonist resiquimod (R848; synthetic analogue single-stranded RNA) or saline nasal spray participants without allergy (n = 12), those allergic rhinitis asthma 11). Immune mediators blood fluid gene expression were monitored over time.ResultsR848 was well tolerated significantly induced IFN-α2a, IFN-γ, proinflammatory cytokines (TNF-α, IL-2, IL-12p70), chemokines (CXCL10, C-C motif chemokine ligand [CCL]2, CCL3, CCL4, CCL13) fluid, causing systemic activation. Participants had increased CCL13 relative participants; induction IFN-stimulated genes DExD/H-box helicase 58, MX dynamin-like GTPase 1, IFN-induced protein tetratricopeptide repeats 3.ConclusionsResponses delivery R848 enables simple assessment responsiveness, revealing that disorders have IFN response RNA R848. This highlights dysregulated mucosa individuals may important determining outcome exposure. Acute measured. We allergy. time. 3. Responses