Increased Concentration of Iodide in Airway Secretions is Associated with Reduced RSV Disease Severity

Abstract

<p>Recent studies have revealed that the human and nonrodent mammalian airway mucosa contains an oxidative host defense system. This three-component system consists of the hydrogen peroxide (H₂O₂)-producing enzymes dual oxidase (Duox)1 and Duox2, thiocyanate (SCN⁻), and secreted lactoperoxidase (LPO). The LPO-catalyzed reaction between H₂O₂ and SCN⁻ yields the bactericidal hypothiocyanite (OSCN⁻) in airway surface liquid (ASL). Although SCN⁻ is the physiological substrate of LPO, the Duox/LPO/halide system can generate hypoiodous acid when the iodide (I⁻) concentration is elevated in ASL. Because hypoiodous acid, but not OSCN⁻, inactivates respiratory syncytial virus (RSV) in cell culture, we used a lamb model of RSV to test whether potassium iodide (KI) could enhance this system <em>in vivo</em>. Newborn lambs received KI by intragastric gavage or were left untreated before intratracheal inoculation of RSV. KI treatment led to a 10-fold increase in ASL I⁻ concentration, and this I⁻ concentration was approximately 30-fold higher than that measured in the serum. Also, expiratory effort, gross lung lesions, and pulmonary expression of an RSV antigen and IL-8 were reduced in the KI-treated lambs as compared with nontreated control lambs. Inhibition of LPO activity significantly increased lesions, RSV mRNA, and antigen. Similar experiments in 3-week-old lambs demonstrated that KI administration was associated with reduced gross lesions, decreased RSV titers in bronchoalveolar lavage fluid, and reduced RSV antigen expression. Overall, these data indicate that high-dose KI supplementation can be used <em>in vivo</em> to lessen the severity of RSV infections, potentially through the augmentation of mucosal oxidative defenses.</p>