Effect Of Roflumilast On Expression Of Th17Cells In Murine Model Of Allergic Rhinitis

Objective Numerous evidences proved Th17cells having potentproinflammatory effect and were involved in the pathogenesis ofautoimmune diseases such as asthma and allergic rhinitis (AR). Roflumilast,a novel selective phosphodiesterase (PDE)-4inhibitor, which possesseseffective anti-inflammatory role by elevating intracellular cAMP content,has been designated as a new medication for COPD. This study aimed toinvestigate the effects of roflumilast on the Th17cells in AR murine models.Methods Mice were averagely divided into3groups: model groups,therapy groups and control groups. The first two groups were induced byclassical method with ovalbumin (OVA) for19days and the therapy groupwas treated with roflumilast during the final2weeks. The control groupsreceived saline injection and challenge instead. The nasal pathologicalchanges were evaluated by immunohistochemistry and hematoxylin eosin(HE) staining methods. The expression of RORγt, IL-17mRNA,IL-22mRNA and RORγtmRNA were respectively measured by western blotand reverse transcription-polymerase chain reaction (RT-PCR).Results The levels of IL-17and IL-22were significantly elevated after systematic challenge in the nasal mucosas. They were reduced afterroflumilast treatment in therapy groups compared with model groups, butstill higher than in control groups. As with IL-17and IL-22, the expressionof RORγt and its mRNA in mucosas were higher in challenged mice andreducing after treatment.Conclusions Roflumilast can inhibit the release of IL-17and IL-22probably by suppressing the expression of RORγt, accordingly blockingTh17differentiation and proliferation in AR mice, suggesting that Th17mayplay a crucial role in the pathology of AR and roflumilast may treat AR byinhibiting Th17differentiation and production.