The tmTNF-α antibody that targets tmTNF-α processing, unlike selective inhibitors of sTNF-α, anti-TNF antibodies, or soluble TNFR, not only reduced sTNF-α levels but also increased tmTNF-α expression and thus effectively prevented AOM/DSS-induced CAC through the inhibition of inflammation and induction of apoptosis, which provides a new insight into the blockade of this pathological process. Here, TNFRSF1A is linked to infectious otitis media.