Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 21 2 2022 04 11 141 150 Yuanfeng Shen Department of Otolaryngology, Traditional Chinese Medical Hospital of Huzhou，Huzhou，Zhejiang, China Entezar Mehrabi Nasab Department of Cardiology, Tehran Heart Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Fatemeh Hassanpour Faculty of Veterinary Medicine, Urmia University, Urmia, Iran Seyyed Shamsadin Athari Department of Immunology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran 2021 09 04 2021 10 23 Current medications to treat allergic rhinitis (AR) include antihistamines, corticosteroids, and anti-leukotrienes. In the present study, we investigated the effects of combination therapy; using these drugs, and evaluates the AR-related markers and parameters in an animal model. After inducing BALB/c mice AR models, the animals were treated with either pranlukast, loratadine, fluticasone, loratadine + fluticasone, loratadine + pranlukast, fluticasone + pranlukast, or loratadine + fluticasone + pranlukast. Clinical symptoms, Immunoglobulin (Ig)G1, ovalbumin (OVA)-specific and total IgE, leukotriene (LT)B4, LTC4, histamine, thymic stromal lymphopoietin (TSLP) serum levels, and interleukin 4 level in the nasal lavage fluid were determined. The expressions of HRH1, CysLT1R, NLR3, Caspase-1, and MUC5a were studied. Allergic symptoms (nasal rubbing and sneezing), serum Igs (IgG1, total and OVA-specific IgE), eicosanoids (LTB4 and LTC4), histamine, TSLP, and IL-4 as well as gene expressions of MUC5a, Caspase-1, NLR3, HRH1, and CysLT1R were reduced in the animals receiving each of the therapeutic regimens; however, more pronounced effects were seen in the group treated with the triple combined protocol (loratadine + fluticasone + pranlukast). The combination of the loratadine, fluticasone, and pranlukast can effectively control the symptoms of AR probably via modulating several related mechanisms at early and late phases of allergic responses. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3347 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3347/1826