Otitis media with effusion in an allergic animal model: A functional and morphological study

Kim, Dong-Kee; Park, Hyu Eun; Back, Sang-A.; Park, Hyang Rim; Kim, Soo Whan; Park, Yooyeon; Yeo, Sang Won; Park, Shi-Nae

doi:10.1016/j.ijporl.2016.02.018

Cited by 17 publications

(6 citation statements)

References 18 publications

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“…20 Th2 cells produce primarily IL-4, IL-5, and IL-13, which play important roles in allergies. 21 Some scholars have reported that high serum IgE expression can upregulate IFN-γ. The IL-13 Arg130Gln genotype affects IFN-γ gene expression via the regulation of the serum IgE level, and plays a role in allergy susceptibility.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-33 and thymic stromal lymphopoietin are primary cytokines involved in the Th1/Th2 inflammatory response in chronic secretory otitis media

et al. 2022

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Background: T-helper (Th)1/Th2 inflammatory responses are responsible for secretory otitis media (SOM) development. However, the mechanisms underlying these immune responses remain unknown. This study aims to identify the primary cytokines that play essential roles in chronic SOM. Methods: Two groups were established for the present study: chronic SOM group ( n = 21) and control group ( n = 10). The middle ear effusion and serum samples of the expression cytokines (interleukin IL-2, IL-4, IL-5, IL-13, IL-17, IL-25, IL-33, interferon [IFN]-γ, thymic stromal lymphopoietin [TSLP], immunoglobulin IgE, and pepsins) were analyzed by enzyme-linked immunosorbent assay. Results: The levels of IL-4, IL-5, IL-13, IL-17, IL-25, IFN-γ, TLSP, pepsins, IL-2, and IL-33 (all, p < 0.001) were higher in middle ear effusion, when compared to those in serum, in chronic SOM group (non-paired sample). However, there was no significant difference in serum expression for those cytokines compared chronic SOM group and control group. The paired sample expression for IL-33 and TLSP (both, p = 0.046) were higher compared the effusion and serum in chronic SOM group. Conclusions: IL-33 produces inflammatory cytokines, such as IL-1b, IL-6, TNF-α, IL-10, IL-4, and TGF-β, which through nucleus into cytoplasm causing inflammatory responses. The present study revealed that IL-33 also produce IL-17, IL-4, IL-5, and IL-13 inflammatory factors, triggering an inflammatory response. Study reported that the combined stimulation of TSLP and IL-33 elicits an approximately 10-fold increase in cytokine production, when compared to the stimulation of IL-33 alone. This suggests that IL-33 and TLSP may be the primary cytokines involved in Th1/Th2 inflammatory responses in chronic SOM.

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Section: Discussionmentioning

confidence: 99%

Interleukin-33 and thymic stromal lymphopoietin are primary cytokines involved in the Th1/Th2 inflammatory response in chronic secretory otitis media

et al. 2022

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“…16,17 The establishment of an OME animal model of allergic reactions has been verified. 18 This study used the immunogenicity of inactivated S. pneumoniae to establish an OME mouse model.…”

Section: Discussionmentioning

confidence: 99%

Surfactant Protein A can Affect the Surface Tension of the Eustachian Tube and Macrophage Migration

Chen

Mao

et al. 2022

The Laryngoscope

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Objective To assess the role and possible mechanism of surfactant protein A (SPA) in the pathogenesis of otitis media with effusion (OME). Methods This was a multi‐part study with both an in vivo mouse model study as well as an in vitro study. The control and study groups (OME group) received phosphate‐buffered saline and inactivated Streptococcus pneumoniae, respectively, via external auditory meatus injections. Changes in the surface tension of secretions from the eustachian tube (ET) and SPA expression were measured in both groups. A transwell assay was performed to observe the effect of different concentrations of SPA on the migration ability of macrophages. We examined the differentially expressed genes related to SPA‐treated macrophages using RNA‐seq analysis. Results On Day 3, the surface tension of the OME group was higher than that of the control group (p = 0.014). The variation intensity of SPA in the ET of the OME group was significantly lower than that of the control group (p < 0.001). Surface tension was correlated with SPA (r = −0.525, p = 0.037). The expression of SPA and macrophages in the ET was different between the two groups. In vitro experiments revealed that macrophages showed different migration abilities with SPA concentration changes (p < 0.05). RNA‐seq and western blotting were performed after macrophages were treated with SPA. The results showed that RhoA and Rac1/2/3 were differentially expressed. Conclusions SPA can change the surface tension of secretions from the ET and affect macrophage migration to alter the function of the ET. Although research in this field of OME is nascent, initial work suggests that SPA likely plays an important role in OME progression. Level of Evidence NA Laryngoscope, 133:1726–1733, 2023

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“…Several mouse models have been generated by utilizing LPS or peptidoglycan-polysaccharides ( Li et al, 2015 ; Zhang et al, 2015 ; Kim et al, 2016 ). Ovalbumin has been used to induce an eosinophilic OM via IN administration in a mouse model or a trans-tympanic injection in a guinea pig model ( Matsubara et al, 2014 ; Kim et al, 2016 ). Moreover, histamine has been used in guinea pigs to induce AOM ( Kozan et al, 2015 ).…”

Section: Om Animal Modelsmentioning

confidence: 99%

Otitis media: recent advances in otitis media vaccine development and model systems

Zahid,

Wilson,

Grice

et al. 2024

Front. Microbiol.

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Otitis media is an inflammatory disorder of the middle ear caused by airways-associated bacterial or viral infections. It is one of the most common childhood infections as globally more than 80% of children are diagnosed with acute otitis media by 3 years of age and it is a common reason for doctor’s visits, antibiotics prescriptions, and surgery among children. Otitis media is a multifactorial disease with various genetic, immunologic, infectious, and environmental factors predisposing children to develop ear infections. Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are the most common culprits responsible for acute otitis media. Despite the massive global disease burden, the pathogenesis of otitis media is still unclear and requires extensive future research. Antibiotics are the preferred treatment to cure middle ear infections, however, the antimicrobial resistance rate of common middle ear pathogens has increased considerably over the years. At present, pneumococcal and influenza vaccines are administered as a preventive measure against otitis media, nevertheless, these vaccines are only beneficial in preventing carriage and/or disease caused by vaccine serotypes. Otitis media caused by non-vaccine serotype pneumococci, non-typeable H. influenza, and M. catarrhalis remain an important healthcare burden. The development of multi-species vaccines is an arduous process but is required to reduce the global burden of this disease. Many novel vaccines against S. pneumoniae, non-typeable H. influenza, and M. catarrhalis are in preclinical trials. It is anticipated that these vaccines will lower the disease burden and provide better protection against otitis media. To study disease pathology the rat, mouse, and chinchilla are commonly used to induce experimental acute otitis media to test new therapeutics, including antibiotics and vaccines. Each of these models has its advantages and disadvantages, yet there is still a need to develop an improved animal model providing a better correlated mechanistic understanding of human middle ear infections, thereby underpinning the development of more effective otitis media therapeutics. This review provides an updated summary of current vaccines against otitis media, various animal models of otitis media, their limitations, and some future insights in this field providing a springboard in the development of new animal models and novel vaccines for otitis media.

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Otitis media with effusion in an allergic animal model: A functional and morphological study

Cited by 17 publications

References 18 publications

Interleukin-33 and thymic stromal lymphopoietin are primary cytokines involved in the Th1/Th2 inflammatory response in chronic secretory otitis media

Interleukin-33 and thymic stromal lymphopoietin are primary cytokines involved in the Th1/Th2 inflammatory response in chronic secretory otitis media

Surfactant Protein A can Affect the Surface Tension of the Eustachian Tube and Macrophage Migration

Otitis media: recent advances in otitis media vaccine development and model systems

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