**6. The role of ascorbic acid in sinonasal immune system**

As an immunomodulatory, antioxidant, and anti-inflammatory agent, ascorbic acid has a potency in sinonasal immune system. Ascorbic acid is known to treat respiratory diseases, including allergic and infectious diseases. The antioxidant effect of ascorbic acid is through scavenging ROS by quick aqueous phase electron transfer and inhibiting lipid peroxidation [24]. The mechanism of ascorbic acid modulates the immune system by influencing the roles of phagocytes, proliferation of T lymphocytes, generation of interferon and cytokine, and gene expression of monocyte adhesion molecules. Besides, it has been proposed that ascorbic acid acts as a biological modulator of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), which is a cAMPdependent chloride channel that modulates respiratory tract epithelial surface fluid production, as well as directing the hydration of mucosal surfaces and providing effective mucociliary clearance. Ascorbic acid was shown to increase chloride generation when applied topically to newly excised sinus and nasal mucosa, indicating a potential application as a pharmaceutical agent to enhance mucociliary clearance [24–27].
