Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 21 2 2022 04 11 119 127 Zhen Wang The second Department of Respiration, Xi'an Children's Hospital, Xi'an, China Lihong Xin The second Department of Respiration, Xi'an Children's Hospital, Xi'an, China Wen Zhang The second Department of Respiration, Xi'an Children's Hospital, Xi'an, China 2021 08 10 2021 09 04 Asthma is a respiratory disease; involving millions of people worldwide. The main cause of asthma is allergy and immune response dysregulation. The effects of azithromycin and doxycycline as asthma-controlling drugs were evaluated in this study. Mice asthma model was produced and asthmatic mice were treated with azithromycin (75 mg/kg, orally) and doxycycline (20 mg/kg, orally). Eosinophils and neutrophils count, interleukin (IL)-4, IL-5, IL-12, IL-13, and total immunoglobulin E (IgE) levels were measured. Histological study and evaluating the genes expression of Muc5ac, Muc5b, IL-33, COX2, MYD88, and TRAF6 were performed. Azithromycin and doxycycline did not affect eosinophil and neutrophil percentage, IL-4, IL-5, IL-12, and total IgE levels, peribronchial and perivascular inflammation, goblet cell hyperplasia, and gene expression of MYD88, TRAF6, and COX2. Treatment with azithromycin significantly decreased IL-13 level, mucus secretion, and gene expression of IL-33, Muc5ac, and Muc5b; compared to the non-treated asthma group. Azithromycin administration controls mucus secretion and inflammation. Azithromycin therapy and not doxycycline might be an effective adjuvant option in asthma with reducing mucus in the airway. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3321 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3321/1823