Otitis Media: Molecular Impact of Inflammation in the Middle and Inner Ear—Cytokines, Steroids, and Ion Homeostasis

MacArthur, Carol J.; Hausman, Frances A.; Kempton, Beth; Lighthall, Jessyka G.; Trune, Dennis R.

doi:10.1002/lary.23818

Cited by 2 publications

(2 citation statements)

References 7 publications

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“…Cytokine genes were also chosen for analysis in this study and include eight key inflammation related cytokines (IL-1α, IL-1β, IL-6, IL-10, CCl3, Cxcl2, CxCl1, and TNFα). These genes have been shown to be very active in the mouse model of otitis media in both the middle and inner ear 1,2,18,20 . Therefore, they were chosen to measure the inner ear inflammatory response to a middle ear steroid injection.…”

Section: Methodsmentioning

confidence: 99%

Intratympanic Steroid Treatments May Improve Hearing via Ion Homeostasis Alterations and Not Immune Suppression

MacArthur¹,

Hausman²,

Kempton³

et al. 2015

Otology &Amp; Neurotology

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Hypothesis The inner ear endothelium is capable of responding to therapeutic steroids by altering local expression of cytokine and ion homeostasis genes that impact inflammation and fluid regulation. Background Glucocorticoids are often given trans-tympanically for hearing disorders because of their anti-inflammatory effects, but their direct impact on inner ear ion homeostasis and cytokine gene expression has not been studied. Methods The middle ears of Balb/c mice were transtympanically injected with 5 µl of either phosphate-buffered saline (PBS), prednisolone or dexamethasone. Untreated mice were used as controls. Mice were euthanized at 6, 24 and 72 hours, the cochleas harvested and total RNA isolated from the inner ear tissues. Expression of eight cytokine genes and 24 ion homeostasis genes were analyzed with qRT-PCR. Results PBS caused upregulation of inflammatory cytokine genes that peaked at 6 hours. Surprisingly, prednisolone and dexamethasone also caused upregulation of most cytokine genes. Interestingly, ion homeostasis genes were predominantly upregulated with dexamethasone and prednisolone, with prednisolone having the larger effect. Conclusion In the murine model, intratympanic steroids caused an initial upregulation of inflammatory cytokine genes in the inner ear, as well as predominantly upregulation of ion homeostasis genes. These findings suggest glucorticoids do not suppress inner ear inflammation, but rather cause an initial inflammatory response in the inner ear. Thus, inflammatory gene suppression is not a likely mechanism for their hearing restorative effects. On the other hand, these steroids have a significant mineralocorticoid function, as demonstrated by increased function of ion homeostasis genes, implicating their ionic and fluid regulatory properties as a mechanism for their therapeutic effects.

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Section: Methodsmentioning

confidence: 99%

Intratympanic Steroid Treatments May Improve Hearing via Ion Homeostasis Alterations and Not Immune Suppression

MacArthur¹,

Hausman²,

Kempton³

et al. 2015

Otology &Amp; Neurotology

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“…Otitis media (OM) is characterised by inflammation of the middle ear and is the most common cause of hearing impairment in children (MacArthur, Hausman, Kempton, Lighthall, & Trune, 2012). Based on variables such as the chronicity of inflammation and the state of middle ear (bulla) fluid, OM is classified into different categories (Myburgh, van Zijl, Swanepoel, Hellström, & Laurent, 2016).…”

Section: Introductionmentioning

confidence: 99%

Cellular content plays a crucial role in Non‐typeableHaemophilus influenzaeinfection of preinflamedJunbomouse middle ear

Vikhe

Purnell

Brown

et al. 2018

Cellular Microbiology

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Non‐typeable Haemophilus influenzae (NTHi) is a major pathogen causing acute otitis media (AOM). The relationship between the cellular content of the middle ear fluid (MEF) during AOM and infection of NTHi is poorly understood. Using the Junbo mouse, a characterised NTHi infection model, we analysed the cellular content of MEF and correlated the data with NTHi titres. The MEF of the Junbo mouse was heterogeneous between ears and was graded from 1 to 5; 1 being highly serous/clear and 5 being heavily viscous/opaque. At seven‐day post‐intranasal inoculation, NTHi was not found in grade‐1 or 2 fluids, and the proportion of MEF that supported NTHi increased with the grade. Analyses by flow cytometry indicated that the cellular content was highest in grade‐4 and 5 fluids, with a greater proportion of necrotic cells and a low‐live cell count. NTHi infection of the middle ear increased the cell count and led to infiltration of immune cells and changes in the cytokine and chemokine levels. Following NTHi inoculation, high‐grade infected MEFs had greater neutrophil infiltration whereas monocyte infiltration was significantly higher in serous noninfected low‐grade fluids. These data underline a role for immune cells, specifically monocytes and neutrophils, and cell necrosis in NTHi infection of the Junbo mouse middle ear.

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Otitis Media: Molecular Impact of Inflammation in the Middle and Inner Ear—Cytokines, Steroids, and Ion Homeostasis

Cited by 2 publications

References 7 publications

Intratympanic Steroid Treatments May Improve Hearing via Ion Homeostasis Alterations and Not Immune Suppression

Intratympanic Steroid Treatments May Improve Hearing via Ion Homeostasis Alterations and Not Immune Suppression

Cellular content plays a crucial role in Non‐typeableHaemophilus influenzaeinfection of preinflamedJunbomouse middle ear

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