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Updated: Nov 7, 2025
Endoscopic Cholesteatoma Surgery
Published on: January 19, 2022
In vitro study on immune response modifiers as novel medical treatment options for cholesteatoma
Tankut Uzun1, Hamdi Çaklı2, Didem Turgut Coşan3
1Department of Otorhinolaryngology, Izmir Bakircay University Cigli Training and Research Hospital, Izmir, Turkey.
Objectives:
To investigate cytokine profile of cholesteatoma and to collect information about important intercellular signaling pathways by establishing two different cell culture models, to block important intercellular signaling pathways in cholesteatoma by applying immune system modifier drugs to develop alternative medical therapy options for cholesteatoma.
Methods:
To observe the pathogenesis of cholesteatoma and to apply the immunomodulatory drugs, cholesteatoma tissue culture models were constituted with HEKa cells and cholesteatoma keratinocytes, which were obtained from 3 patients who underwent operations for cholesteatoma. Medicines including 5-fluorourasil, imiquimod, cyclosporine, and tacrolimus were applied on both cholesteatoma keratinocytes and HEKa cells. After 48 h of incubation, IL-1, IL-6, IL-8, IL-10, TNF-α, and Ki67 levels were measured to determine cell viability rates.
Results:
In the cholesteatoma control group, IL-6 and TNF-α levels were found higher than in the HEKa control group. All repurposed drugs in the study demonstrated anti-inflammatory, anti-proliferative, and cytotoxic effects on cholesteatoma. Imiquimod and tacrolimus in particular are potential treatment prospects for cholesteatoma due to their strong anti-inflammatory and cytotoxic effects.
Conclusion:
Medical therapy options for cholesteatoma are still missing and surgery is not the ultimate solution. We have focused on intercellular inflammatory processes, which play significant roles in the pathogenesis of cholesteatoma in our paper. Inflammation and proliferation of cholesteatoma decreased after all repurposed drug applications in our study. Anti-inflammatory and anti-proliferative effects of tacrolimus and imiquimod was more significant than other drugs in the study. For this reason, tacrolimus and imiquimod should be examined in depth with in vivo studies in terms of efficacy and safety for medical treatment of cholesteatoma.
Insights
This study explored new medical treatments for cholesteatoma by testing immune system drugs on cell cultures. Imiquimod and tacrolimus showed significant anti-inflammatory and anti-proliferative effects, suggesting potential as alternative therapies.
Area of Science:
- Otolaryngology
- Dermatology
- Immunology
Background:
- Cholesteatoma pathogenesis involves complex intercellular signaling and inflammation.
- Current surgical treatments for cholesteatoma are not always definitive.
- Novel medical therapies are needed to address cholesteatoma's inflammatory and proliferative nature.
Purpose of the Study:
- To investigate the cytokine profile of cholesteatoma.
- To establish cell culture models for studying cholesteatoma.
- To evaluate immune system modifier drugs as potential medical therapies for cholesteatoma.
Main Methods:
- Established cholesteatoma keratinocyte and HEKa cell culture models.
- Applied immunomodulatory drugs (5-fluorouracil, imiquimod, cyclosporine, tacrolimus).
- Measured cytokine levels (IL-1, IL-6, IL-8, IL-10, TNF-α) and Ki67 after 48 hours.
Main Results:
- Cholesteatoma tissues exhibited higher IL-6 and TNF-α levels compared to controls.
- All tested drugs demonstrated anti-inflammatory, anti-proliferative, and cytotoxic effects.
- Imiquimod and tacrolimus showed particularly strong anti-inflammatory and cytotoxic properties.
Conclusions:
- Repurposed drugs, especially imiquimod and tacrolimus, significantly reduced cholesteatoma inflammation and proliferation in vitro.
- These findings support further in vivo investigation of tacrolimus and imiquimod for cholesteatoma medical treatment.
- Developing effective medical therapies could offer alternatives or adjuncts to surgery for cholesteatoma.
