Hereby, the results were analogous to the proliferation assay, since (1) HMGB1 stimulated the production of IL-6; (2) sEVs isolated from the plasma of controls or cholesteatoma patients stimulated the production of IL-6 even more; (3) cholesteatoma patient-derived sEVs stimulated the production of IL-6 significantly more compared to control-derived sEVs (p < 0.05); (4) the induction of IL-6 production was effectively blocked by the RAGE-specific antibody; and (5) the results were consistent for both keratinocyte cell lines (Figure 4C). Here, HMGB1 is linked to cholesteatoma.