Increased Concentration of Iodide in Airway Secretions Is Associated with Reduced Respiratory Syncytial Virus Disease Severity

Derscheid, Rachel J.; Geelen, Albert G. Van; Berkebile, Abigail R.; Gallup, Jack M.; Hostetter, Shannon Jones; Bánfi, Botond; McCray, Paul B.; Ackermann, Mark R.

doi:10.1165/rcmb.2012-0529oc

Cited by 45 publications

(69 citation statements)

References 43 publications

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“…Because of its similarity to human respiratory syncytial virus (hRSV), BRSV was not examined in this study. BRSV was not examined in vitro in this study because of the previous reports of inactivation of hRSV in both in vitro studies and an in vivo challenge model in sheep of the LPO/H 2 O 2 /I − . In the in vivo challenge model, lambs administered KI had decreased gross pulmonary lesions, viral antigen concentration, and clinical signs of respiratory disease compared to controls .…”

Section: Discussionmentioning

confidence: 99%

“…The submucosal glands required for this reaction are not present equally in all mammals. Humans, sheep, and cattle have submucosal glands, rats have few present, and smaller mammals lack submucosal glands . A recent discovery in sheep and humans is that the oxidative antimicrobial system not only catalyzes SCN − to OSCN − but can also produce hypoiodous acid (HOI) from iodine (I).…”

mentioning

confidence: 99%

“…When I is supplemented as a single, high‐dose bolus, iodide (I − ) secretion in the upper respiratory tract increases. As I − concentration increases in the ASL, SCN − concentration decreases, indicating that I − and SCN − compete for secretion into the respiratory tract . Hypoiodous acid has potent antimicrobial activity .…”

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confidence: 99%

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Efficacy of Oral Administration of Sodium Iodide to Prevent Bovine Respiratory Disease Complex

Shoemake

Ley

Newcomer

et al. 2018

Veterinary Internal Medicne

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BackgroundThe prevention of bovine respiratory disease complex (BRD) in beef cattle is important to maintaining health and productivity of calves in feeding operations.ObjectiveDetermine whether BRD bacterial and viral pathogens are susceptible to the lactoperoxidase/hydrogen peroxide/iodide (LPO/H2O2/I−) system in vitro and to determine whether the oral administration of sodium iodide (NaI) could achieve sufficient concentrations of iodine (I) in the respiratory secretions of weaned beef calves to inactivate these pathogens in vivo.AnimalsSixteen weaned, apparently healthy, commercial beef calves from the University of Missouri, College of Veterinary Medicine teaching herd.MethodsIn vitro viral and bacterial assays were performed to determine susceptibility to the LPO/H2O2/I− system at varying concentrations of NaI. Sixteen randomly selected, healthy crossbred beef weanlings were administered 70 mg/kg NaI, or water, orally in a blinded, placebo‐controlled trial. Blood and nasal secretions were collected for 72 hours and analyzed for I− concentration.ResultsBovine herpesvirus‐1, parainfluenza‐3, Mannheimia haemolytica and Bibersteinia trehalosi were all inactivated or inhibited in vitro by the LPO/H2O2/I− reaction. Oral administration of NaI caused a marked increase in nasal fluid I concentration with a C max = 181 (1,420 μM I), T12, a sufficient concentration to inactivate these pathogens in vitro.Conclusions and Clinical ImportanceIn vitro, the LPO/H2O2/I− system inactivates and inhibits common pathogens associated with BRD. The administration of oral NaI significantly increases the I concentration of nasal fluid indicating that this system might be useful in preventing bovine respiratory infections.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Efficacy of Oral Administration of Sodium Iodide to Prevent Bovine Respiratory Disease Complex

Shoemake

Ley

Newcomer

et al. 2018

Veterinary Internal Medicne

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“…This possibility is consistent with a previous study in bronchial epithelial cells showing that IL-4/IL-13-mediated SLC26A4 induction via direct promoter transactivation by the JAK1-STAT6 pathway (66,67) is associated with increased SCN -apical transport (57). In the presence of H 2 O 2 produced by Duox, SCN -is oxidized in the microbicide compound hypothyocyanite (OSCN -) by mucosal lactoperoxidase, which plays an important role in innate immunity (68,69).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Interleukin-4 in the Thyroid of Transgenic Mice Upregulates the Expression ofDuox1and the Anion Transporter Pendrin

Eskalli

Achouri

Hahn

et al. 2016

Thyroid

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Background:The dual oxidases (Duox) are involved in hydrogen peroxide generation, which is essential for thyroid hormone synthesis, and therefore they are markers of thyroid function. During inflammation, cytokines upregulate DUOX gene expression in the airway and the intestine, suggesting a role for these proteins in innate immunity. It was previously demonstrated that interleukin-4 (IL-4) upregulates DUOX gene expression in thyrocytes. Although the role of IL-4 in autoimmune thyroid diseases has been studied extensively, the effects of IL-4 on thyroid physiology remain largely unknown. Therefore, a new animal model was generated to study the impact of IL-4 on thyroid function. Methods: Transgenic (Thyr-IL-4) mice with thyroid-targeted expression of murine IL-4 were generated. Transgene expression was verified at the mRNA and protein level in thyroid tissues and primary cultures. The phenotype of the Thyr-IL-4 animals was characterized by measuring serum thyroxine (T4) and thyrotropin levels and performing thyroid morphometric analysis, immunohistochemistry, whole transcriptome sequencing, quantitative reverse transcription polymerase chain reaction, and ex vivo thyroid function assays. Results: Thyrocytes from two Thyr-IL-4 mouse lines (#30 and #52) expressed IL-4, which was secreted into the extracellular space. Although 10-month-old transgenic animals had T4 and thyrotropin serum levels in the normal range, they had altered thyroid follicular structure with enlarged follicles composed of elongated thyrocytes containing numerous endocytic vesicles. These follicles were positive for T4 staining the colloid, indicating their capacity to produce thyroid hormones. RNA profiling of Thyr-IL-4 thyroid samples revealed modulation of multiple genes involved in inflammation, while no major leukocyte infiltration could be detected. Upregulated expression of Duox1, Duoxa1, and the pendrin anion exchanger gene (Slc26a4) was detected. In contrast, the iodide symporter gene Slc5a5 was markedly downregulated resulting in impaired iodide uptake and reduced thyroid hormone levels in transgenic thyroid tissue. Hydrogen peroxide production was increased in Thyr-IL-4 thyroid tissue compared with wild-type animals, but no significant oxidative stress could be detected. Conclusions: This is the first study to show that ectopic expression of IL-4 in thyroid tissue upregulates Duox1/ Duoxa1 and Slc26a4 expression in the thyroid. The present data demonstrate that IL-4 could affect thyroid morphology and function, mainly by downregulating Slc5a5 expression, while maintaining a normal euthyroid phenotype.

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“…Moreover, recent studies have shown that iodide may play an important role in the innate immune system of the pulmonary tree by acting as a substrate for an oxidative microbicidal system [6,7]. Iodine accumulation in bronchopulmonary secretions, while acting to defend against respiratory viruses and bacteria in inflammatory lung states [6][7][8][9][10], may also lead to false-positive post-RAI scans resulting in erroneous diagnoses.…”

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confidence: 99%

False-Positive Radioactive Iodine Uptake Mimicking Miliary Lung Metastases in a Patient Affected by Papillary Thyroid Cancer and IgA Deficiency

Demidowich

Kundu

Reynolds

et al. 2015

Nucl Med Mol Imaging

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A 42-year-old female with immunoglobulin A deficiency and recurrent sinopulmonary infections underwent thyroidectomy for papillary thyroid cancer (PTC). I scintigraphy demonstrated diffuse pulmonary uptake, suggesting metastatic disease. However, subsequent pathologic, biochemical and radiographic testing proved that she was in fact disease free, and the initial 123 I pulmonary uptake was identified as a false positive. Inflammatory conditions may rarely cause iodine uptake in non-thyroidal tissues due to local retention, organification, and/or immunologic utilization. To avoid exposing patients to unnecessary treatments, it is critical for clinicians to recognize that comorbid pulmonary conditions may mimic metastatic PTC on radioiodine scintigraphy.Keywords Radionuclide imaging . Scintigraphy . Papillary thyroid carcinoma . False-positive reactions . IgA deficiency A 42-year-old female, with a past medical history of IgA deficiency and recurrent sinopulmonary infections, underwent total thyroidectomy for a 1.1-cm follicular variant PTC. Preoperative ultrasound (US) found no abnormal lymph nodes, and pathology demonstrated a welldifferentiated unifocal cancer with no capsular or lymphovascular invasion. At 3-month follow-up, the rhTSH-stimulated Tg level was low at 1.7 ng/ml with negative Tg antibodies. However, the 123 I whole-body scan demonstrated focal increased uptake in the left thyroid bed and diffuse uptake in both lungs, suggestive of metastatic disease (Fig. 1a). At the time of testing, the patient was taking oral prednisone, inhaled mometasone/formoterol, and oral amoxicillin/clavulanate for a bronchitis flare. Given her conflicting results, the possibility of a false-positive radioiodine uptake result in the setting of active pulmonary inflammation was raised. In view of these findings, the patient was scheduled for 131 I dosimetry after levothyroxine withdrawal. Imaging at 48 h confirmed the thyroid bed findings, but the lungs had only minimal uptake (Fig. 1b). Labwork demonstrated an appropriately elevated TSH of 67.3 mcIU/ml, with a low Tg of 4.6 ng/ml, and negative Tg antibodies. These results suggested that the initial pulmonary uptake was a false positive. The patient was subsequently treated with 100 mCi of 131 I. The post-treatment scan (Fig. 1c) confirmed the pretreatment findings.At 1-year follow-up, the rhTSH-stimulated 123 I scan again showed faint diffuse uptake in both lungs. Stimulated Tg and Tg antibody levels were undetectable, neck US was negative for residual or recurrent disease, and CT of the lungs demonstrated bilateral bronchiectasis with no obvious metastatic lesions (Fig. 2). Thus, the persistent radioiodine uptake in the lungs was confirmed to be a spurious finding due to her underlying pulmonary disease rather than metastatic thyroid cancer.

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Increased Concentration of Iodide in Airway Secretions Is Associated with Reduced Respiratory Syncytial Virus Disease Severity

Cited by 45 publications

References 43 publications

Efficacy of Oral Administration of Sodium Iodide to Prevent Bovine Respiratory Disease Complex

Efficacy of Oral Administration of Sodium Iodide to Prevent Bovine Respiratory Disease Complex

Overexpression of Interleukin-4 in the Thyroid of Transgenic Mice Upregulates the Expression ofDuox1and the Anion Transporter Pendrin

False-Positive Radioactive Iodine Uptake Mimicking Miliary Lung Metastases in a Patient Affected by Papillary Thyroid Cancer and IgA Deficiency

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