TNF and hand, foot and mouth disease: The results showed that after CV-A16 infection, IP-10 can be activated through the PRR-mediated pathways, and then IP-10 induced TNF-α production leads to BBB permeability alteration via destroying the intercellular connection at the BBB; thereby these findings suggest that the IP-10/TNF-α cytokine axis can be considered as a new marker for early diagnosis in CV-A16-infected HFMD patients, as well as a potential target for developing novel therapies for CV-A16-infected HFMD patients.