In vitro study on immune response modifiers as novel medical treatment options for cholesteatoma

Abstract

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-alpha, and Ki67 levels were measured to determine cell viability rates. Results: In the cholesteatoma control group, IL-6 and TNF-alpha 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.